The complex hexaploid oil-Camellia genome traces back its phylogenomic history and multi-omics analysis of Camellia oil biosynthesis.

Oil-Camellia (Camellia oleifera), belonging to the Theaceae family Camellia, is an important woody edible oil tree species. The Camellia oil in its mature seed kernels, mainly consists of more than 90% unsaturated fatty acids, tea polyphenols, flavonoids, squalene and other active substances, which is one of the best quality edible vegetable oils in the world. However, genetic research and molecular breeding on oil-Camellia are challenging due to its complex genetic background. Here, we successfully report a chromosome-scale genome assembly for a hexaploid oil-Camellia cultivar Changlin40. This assembly contains 8.80 Gb genomic sequences with scaffold N50 of 180.0 Mb and 45 pseudochromosomes comprising 15 homologous groups with three members each, which contain 135 868 genes with an average length of 3936 bp. Referring to the diploid genome, intragenomic and intergenomic comparisons of synteny indicate homologous chromosomal similarity and changes. Moreover, comparative and evolutionary analyses reveal three rounds of whole-genome duplication (WGD) events, as well as the possible diversification of hexaploid Changlin40 with diploid occurred approximately 9.06 million years ago (MYA). Furthermore, through the combination of genomics, transcriptomics and metabolomics approaches, a complex regulatory network was constructed and allows to identify potential key structural genes (SAD, FAD2 and FAD3) and transcription factors (AP2 and C2H2) that regulate the metabolism of Camellia oil, especially for unsaturated fatty acids biosynthesis. Overall, the genomic resource generated from this study has great potential to accelerate the research for the molecular biology and genetic improvement of hexaploid oil-Camellia, as well as to understand polyploid genome evolution.

Stellate ganglion block for visceral pain in elderly patients undergoing video-assisted thoracoscopic lung cancer surgery: a randomized, controlled trial.

BACKGROUND: Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS). METHODS: A prospective, randomized, controlled trial enrolled 77 elderly patients undergoing VATS. Patients were randomized to SGB followed by modified intercostal nerve block (Group S, n=37); or modified intercostal nerve block only (Group C, n=40). Remifentanil 0.02-0.2 µg·kg-1·min-1 was titrated to keep pain threshold index values between 40-65 and maintain mean arterial pressure or heart rate values around 20% of baseline values. Patient-controlled intravenous analgesia with sufentanil was used in the postoperative period. The co-primary outcomes were the perioperative cumulative opioid consumption and pain scores on movement at 24 h after surgery. RESULTS: Compared with control group, SGB greatly reduced the intraoperative remifentanil consumption[300.00(235.00-450.00)µg versus 710.00(500.00-915.00)µg; P<0.01], with no difference in cumulative sufentanil consumption to 48h post-surgery. There was a statistically significant difference in pain scores on movement at 24h between groups [4.00(3.00-4.00) versus 4.00(3.25-5.00); P=0.01]. Further exploratory analyses showed significant difference for intra-chest pain on movement at 24h [3.00(2.00-3.00) versus 3.00(2.25-4.00); P=0.01]. No significant difference was observed in nausea/vomiting, time to pass flatus and postoperative length of stay. CONCLUSION: Preoperative stellate ganglion blocks for elderly patients could effectively blunt intraoperative visceral stress and reduce postoperative visceral pain extending 24 h after VATS. This initial finding deserve further investigation.

Thyroid stimulating receptor autoantibodies.

Thyroid-stimulating hormone receptor autoantibodies (TRAbs) play a crucial role as pathogenic antibodies in both the diagnosis and management of Graves' disease (GD). GD, an autoimmune disease resulting from a combination of genetic and environmental factors, is the most common cause of hyperthyroidism. With advancements in technology for TRAb detection and the availability of automated commercial kits, TRAb has become an essential clinical laboratory marker for the diagnosis of GD, as well as extra-thyroidal manifestations like Graves' ophthalmopathy (GO). This article provides a comprehensive review of TRAb, encompassing its clinical assays along with its significance in the clinical setting.

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.

Synchronous Driving Method for Stitching Pixel Arrays Based on an Adaptive Correction Technique.

With the application of stitching technology in large-pixel-array CMOS image sensors, the problem of non-synchronized output signals from pixel array bilateral driver circuits has become progressively more serious and has led to the DC perforation of bilateral driver circuits, while conventional clock tree synchronization design methodology does not apply to stitching technology. Therefore, this paper analyses reasons for the inconsistency in the output signals of bilateral driving circuits and proposes a synchronous driving method applicable to stitching pixel arrays based on the idea of on-chip output signal delay detection and calibration. This method detects and corrects the non-synchrony of the row driver output signals on both sides according to changes in the operating environment of the chip. This method is characterized by a simple structure and high reliability. Finally, based on the 55 nm stitching process, simulations are carried out in a CMOS image sensor with a chip area of 77 mm × 84 mm to verify that this method is feasible. This large image sensor with a 150 M pixel array has a frame rate of over 10 FPS.

Asymptomatic elevation of parathyroid hormone levels by antibodies against reagent alkaline phosphatase.

CONTEXT: Although immunoassay interference is a well-known phenomenon, its detection in routine clinical practice remains challenging. Most immunoassay interference can be attributed to the presence of heterophilic or anti-hormone antibodies. However, reports on immunoassay interference specifically related to parathyroid hormone (PTH) are scarce. CASE DESCRIPTION: A 77-year-old woman with hypertension, nephrotic syndrome, and high PTH levels for one year was admitted to our Surgical Department for treatment. The patient had no specific symptoms and normal calcium and alkaline phosphatase (ALP) levels but markedly elevated PTH levels. PTH was 2172 pg/mL using the Beckman Coulter system, whereas the Roche, Abbot, and Siemens systems yielded normal results. PTH concentration decreased to 63.8 pg/mL after pretreatment with polyethylene glycol 6000 and did not decrease to normal levels following pretreatment with heterophilic blocking tube-50 (HBT-50), heterophilic blocking reagent (HBR)-21, or HBR-25. When the HBR-21 concentration was increased, serum PTH decreased to 99.0 pg/mL. After treatment with scavenger bovine alkaline phosphatase (inactive), the concentration of PTH decreased to a normal value (51.3 pg/mL). Additionally, PTH (1-84) concentration was 17.6 pg/mL using LC-MS/MS. CONCLUSION: PTH was falsely evaluated due to anti-bovine ALP antibodies (antibodies against reagent ALP). Anti-bovine ALP antibodies should be considered in assays that use ALP as a signal generator.

Association between perioperative self-reported sleep disturbances and delirium risk in elderly patients following total joint arthroplasty: a cohort study.

Perioperative sleep disturbance may increase delirium risk. However, the role of perioperative sleep disturbance in delirium following total joint arthroplasty remains unclear. This prospective cohort study aimed to observe the delirium risk in patients with sleep disturbances. After excluding pre-existing sleep disturbances, older patients scheduled for total joint arthroplasty from July 17, 2022, to January 12, 2023, were recruited. Preoperative sleep disturbance or postoperative sleep disturbance was defined as a Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) score of <50 during hospitalisation. A cut-off score of 25 was used to classify the severity of sleep disturbance. The primary outcome was the incidence of postoperative delirium. In all, 11.6% of cohort patients (34/294) developed delirium. After multivariate analysis, a preoperative Day 1 RCSQ score of ≤25 (odds ratio [OR] 3.62, 95% confidence interval [CI] 1.19-10.92; p = 0.02), occurrence of sleep disturbances (OR 2.76, 95% CI 1.19-6.38; p = 0.02) and RCSQ score of ≤25(OR 2.91, 95% CI 1.33-6.37; p = 0.007) postoperatively were strong independent predictors of delirium. After sensitivity analysis for daily delirium, a postoperative Day 1 RCSQ score of ≤25 (OR 9.27, 95% CI 2.72-36.15; p < 0.001) was associated with a greater risk of delirium on postoperative Day 1, with a reasonable discriminative area under the curve of 0.730. We concluded that postoperative but not preoperative sleep disturbances may be an independent factor for delirium risk. Sleep disturbance on the first night after surgery was a good predictor of subsequent delirium, no matter the nature of self-reported sleep disturbance.

Whole-course application of dexmedetomidine as an adjuvant to spinal-epidural anesthesia for cesarean section: A randomized, controlled trial.

Background: Dexmedetomidine is known to prolong the analgesic duration of spinal anesthesia, but it can be challenging to achieve further extension without opioids. Therefore, this study aimed to investigate a novel analgesic strategy using dexmedetomidine as an adjuvant to spinal-epidural anesthesia for elective cesarean surgery. Methods: The study was a randomized, double-blind, controlled trial conducted at a single center. Sixty parturients who underwent elective cesarean were randomly assigned to either group C or group D. Group D received an intrathecal injection of 12.5 mg ropivacaine and 5 µg dexmedetomidine followed by continuous epidural patient-controlled analgesia (PCA) infusion with a total volume of 100 ml, containing 0.2 % ropivacaine and 0.5 µg/kg dexmedetomidine. Group C received an intrathecal injection of 12.5 mg ropivacaine with an equivalent saline placebo followed by a similar PCA infusion, containing 0.2 % ropivacaine and an equivalent saline placebo. Results: The primary outcome was visual analog scale score on movement at 24 h after surgery. The results showed that the rest and motion pain scores in group D were significantly lower than those in group C at 6 h, 12 h, and 24 h after surgery (P < 0.05), with the differences at 24 h were 5.0 (5.0, 5.0)in group D versus 5.0 (5.0, 6.0) in group C (P = 0.04). Additionally, the time to the first PCA in group D was significantly longer than that in group C (P < 0.05), as well as the time of sensory and motor recovery. Conclusions: Whole-course application of dexmedetomidine as an adjuvant to spinal-epidural anesthesia could effectively extend the analgesic duration of ropivacaine to 24 h following elective cesarean surgery.

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.

Evolution of LC-MS/MS in clinical laboratories.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has attracted significant attention in clinical practice owing to its numerous advantages. However, the widespread adoption of this technique is hindered by certain limitations, such as inappropriate analyte selection, low levels of automation, and a lack of specific reference intervals and quality control programs. This review comprehensively summarizes the current challenges associated with LC-MS/MS and proposes potential resolutions. The principle of utility should guide the selection of biomarkers, prioritizing their practical value over sheer quantity. To achieve full-process automation, methodological innovation is crucial for developing high-throughput equipment. Establishing reference intervals for mass spectrometry-based assays across multiple centers and diverse populations is essential for accurate result interpretation. Additionally, the development of commercial quality control materials assumes pivotal importance in ensuring assay reliability and reproducibility. Harmonization and standardization efforts should focus on the development of reference methods and materials for the clinical use of LC-MS/MS. In the future, commercial assay kits and laboratory-developed tests (LDTs) are expected to coexist in clinical laboratories, each offering distinct advantages. The collaborative efforts of diverse professionals is vital for addressing the challenges associated with the clinical application of LC-MS/MS. The anticipated advancements include simplification, increased automation, intelligence, and the standardization of LC-MS/MS, ultimately facilitating its seamless integration into clinical routines for both technicians and clinicians.

Establishment of a reference interval for total carbon dioxide using indirect methods in Chinese populations living in high-altitude areas: A retrospective real-world analysis.

BACKGROUND: Hypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China. METHODS: Anonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI. RESULTS: A total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14-24 mmol/L (calculated using Hoffmann and refineR) and 15-24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14-25 mmol/L (calculated using Hoffmann and Bhattacharya), 16-23 mmol/L (EM), 15-24 mmol/L (kosmic), and 14.2-24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14-24 mmol/L (calculated using Hoffmann and refineR), 15-24 mmol/L (Bhattacharya and kosmic), and 15-23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22-29 mmol/L) that was provided by the manufacturer. CONCLUSION: The tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet.

The α2 Adrenoceptor Agonist and Sedative/Anaesthetic Dexmedetomidine Excites Diverse Neuronal Types in the Ventrolateral Preoptic Area of Male Mice.

SUMMARY STATEMENT: Dexmedetomidine is an important ICU sedative. The mechanism of dexmedetomidine is not fully understood. Activating NA(-) and NA(+) neurons in the VLPO by dexmedetomidine using polysomnography and electrophysiological recording, this may explain the unique sedative properties with rapid arousal.

Liquid chromatography-tandem mass spectrometry in fat-soluble vitamin deficiency.

Fat-soluble vitamins, including vitamins A, D, E, and K, are essential for maintaining normal body function and metabolism. Fat-soluble vitamin deficiency may lead to bone diseases, anemia, bleeding, xerophthalmia, etc. Early detection and timely interventions are significant for preventing vitamin deficiency-related diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is developing into a potent instrument for the precise detection of fat-soluble vitamins due to its high sensitivity, high specificity, and high resolution.

A Novel Opioid-Sparing Analgesia Following Thoracoscopic Surgery: A Non-Inferiority Trial.

Purpose: This randomized, non-inferiority study aimed to observe the feasibility of opioid-sparing analgesia based on modified intercostal nerve block (MINB) following thoracoscopic surgery. Patients and Methods: 60 patients scheduled for single-port thoracoscopic lobectomy were randomized to the intervention group or control group. After MINB was performed in both groups at the end of the surgery, the intervention group received patient controlled-intravenous analgesia (PCIA) of dexmedetomidine 0.05 µg/kg/h for 72 h after surgery, and the control group received conventional PCIA of sufentanil 3 µg/kg for 72 h. The primary outcome was a visual analog scale (VAS) on coughing 24 h after surgery. Secondary outcomes included the time to first analgesic request, pressing times of PCIA, time to first flatus, and hospital stay. Results: There was no difference in the cough-VAS at 24 h (median [interquartile range]) between the intervention group [3 (2-4)] and control group [3 (2-4), P = 0.36]. The median difference (95% CI) in the cough-VAS at 24 h was [0 (0 to 1), P = 0.36]. There was no significant difference in the time to first analgesic request, pressing times of PCIA, and hospital stay between groups (P > 0.05). A significant decrease in time to first flatus was observed in the intervention group (P < 0.01). Conclusion: Opioid-sparing analgesia provided safe and analogous postoperative analgesia with a shortened time to first flatus, compared with sufentanil-based analgesia in thoracoscopic surgery. This might be a novel method recommended for thoracoscopic surgery.

Utilization of five data mining algorithms combined with simplified preprocessing to establish reference intervals of thyroid-related hormones for non-elderly adults.

BACKGROUND: Despite the extensive research on data mining algorithms, there is still a lack of a standard protocol to evaluate the performance of the existing algorithms. Therefore, the study aims to provide a novel procedure that combines data mining algorithms and simplified preprocessing to establish reference intervals (RIs), with the performance of five algorithms assessed objectively as well. METHODS: Two data sets were derived from the population undergoing a physical examination. Hoffmann, Bhattacharya, Expectation Maximum (EM), kosmic, and refineR algorithms combined with two-step data preprocessing respectively were implemented in the Test data set to establish RIs for thyroid-related hormones. Algorithm-calculated RIs were compared with the standard RIs calculated from the Reference data set in which reference individuals were selected following strict inclusion and exclusion criteria. Objective assessment of the methods is implemented by the bias ratio (BR) matrix. RESULTS: RIs of thyroid-related hormones are established. There is a high consistency between TSH RIs established by the EM algorithm and the standard TSH RIs (BR = 0.063), although EM algorithms seems to perform poor on other hormones. RIs calculated by Hoffmann, Bhattacharya, and refineR methods for free and total triiodo-thyronine, free and total thyroxine respectively are close and match the standard RIs. CONCLUSION: An effective approach for objectively evaluating the performance of the algorithm based on the BR matrix is established. EM algorithm combined with simplified preprocessing can handle data with significant skewness, but its performance is limited in other scenarios. The other four algorithms perform well for data with Gaussian or near-Gaussian distribution. Using the appropriate algorithm based on the data distribution characteristics is recommended.

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of Patients With Diabetes Insipidus: A Systematic Review and Meta-analysis.

OBJECTIVE: Accurate diagnosis of diabetes insipidus (DI) is of significant importance for correct management. We aimed to evaluate the diagnostic accuracy of copeptin level measurements in the differential diagnosis between DI and primary polydipsia (PP). METHODS: A literature search of electronic databases from January 1, 2005, to July 13, 2022, was performed. Primary studies that evaluated the diagnostic accuracy of copeptin concentration in patients with DI and PP were considered eligible. Two reviewers independently screened relevant articles and extracted data. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the quality of the included studies. The hierarchical summary receiver operating characteristic model and bivariate method were used. RESULTS: Seven studies including 422 patients with polydipsia-polyuria syndrome were included; of the 422 patients, 189 (44.79%) presented with arginine vasopressin deficiency (AVP-D, cranial DI) and 212 (50.24%) with PP. The summary estimates of the diagnostic performance of stimulated copeptin to differentiate between PP and AVP-D were 0.93 (95% CI, 0.89-0.97) for sensitivity and 0.96 (95% CI, 0.88-1.00) for specificity. Baseline copeptin level showed high performance in identifying AVP resistance (nephrogenic DI), with a pooled sensitivity of 1.00 (95% CI, 0.82-1.00) and specificity of 1.00 (95% CI, 0.98-1.00); however, it showed little value in the differentiation between PP and AVP-D. CONCLUSION: Copeptin level measurement is a useful tool for the differential diagnosis of patients with DI and PP. Stimulation before copeptin measurement is necessary in the diagnosis of AVP-D.

Activation of the PACAP/PAC1 Signaling Pathway Accelerates the Repair of Impaired Spatial Memory Caused by an Ultradian Light Cycle.

The mechanism of light-induced spatial memory deficits, as well as whether rhythmic expression of the pituitary adenylyl cyclase-activating polypeptides (PACAP)-PAC1 pathway influenced by light is related to this process, remains unclear. Here, we aimed to investigate the role of the PACAP-PAC1 pathway in light-mediated spatial memory deficits. Animals were first housed under a T24 cycle (12 h light:12 h dark), and then light conditions were transformed to a T7 cycle (3.5 h light:3.5 h dark) for at least 4 weeks. The spatial memory function was assessed using the Morris water maze (MWM). In line with behavioral studies, rhythmic expression of the PAC1 receptor and glutamate receptors in the hippocampal CA1 region was assessed by western blotting, and electrophysiology experiments were performed to determine the influence of the PACAP-PAC1 pathway on neuronal excitability and synaptic signaling transmission. Spatial memory was deficient after mice were exposed to the T7 light cycle. Rhythmic expression of the PAC1 receptor was dramatically decreased, and the excitability of CA1 pyramidal cells was decreased in T7 cycle-housed mice. Compensation with PACAP1-38, a PAC1 receptor agonist, helped T7 cycle-housed mouse CA1 pyramidal cells recover neuronal excitability to normal levels, and cannulas injected with PACAP1-38 shortened the time to find the platform in MWM. Importantly, the T7 cycle decreased the frequency of AMPA receptor-mediated excitatory postsynaptic currents. In conclusion, the PACAP-PAC1 pathway is an important protective factor modulating light-induced spatial memory function deficits, affecting CA1 pyramidal cell excitability and excitatory synaptic signaling transmission.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

BACKGROUND: Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. PURPOSE: To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. METHODS: We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. RESULTS: The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. CONCLUSIONS: The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management.

BACKGROUND: We developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. METHODS: AUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. RESULTS: AUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). CONCLUSIONS: The total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

Total serum vitamin B12 (cobalamin) LC-MS/MS assay as an arbiter of clinically discordant immunoassay results.

OBJECTIVES: Measurement of the serum levels of vitamin B12 (VB12) is key for evaluating VB12 deficiency-dependent anemia. Immunoassay, the major method for determining VB12, tends to give false-normal results because of the presence of anti-intrinsic factor (IF-Ab) or other factors such as heterophilic antibodies et al. This study aimed to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method that is helpful for distinguish false normal VB12 results measured by the immunoassay. METHODS: Different forms of VB12 were derivatized into CN-B12, which was collected through solid-phase extraction and analyzed via LC-MS/MS. 236 serum samples were measured both by LC-MS/MS and immunoassay, results were compared, and the IF-Ab effect was evaluated. RESULTS: The LC-MS/MS assay afforded a linear slope from 20 to 4,000 pmol/L for CN-B12. OH-VB12, methyl-VB12, and CoA-VB12 showed recovery within 89.3-109.5%. The intra-assay CV of VB12 was 2.6-4.1%, whereas the total CV was 9.3-9.8%. Passing-Bablok regression between LC-MS/MS and immunoassay results showed that the slope was 1.085 and the intercept was -15.691. The Bland-Altman plot showed that the mean difference and difference% were -34.6 pmol/L and 0.3%, respectively. Inter-rater agreement analysis showed that the linear weighted kappa value was 0.885, implying good agreement between the two methods. However, two samples were falsely elevated and one sample was falsely normal in the immunoassay compared with LC-MS/MS. The LC-MS/MS method helped in the distinction of false-normal VB12 results shown by the immunoassay. CONCLUSIONS: The VB12 LC-MS/MS method can be used as an arbiter of clinically discordant immunoassay results.