Current status of emergency medical service use in ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: The mortality rate of myocardial infarction in China has increased dramatically in the past three decades. Although emergency medical service (EMS) played a pivotal role for the management of patients with ST-segment elevation myocardial infarction (STEMI), the corresponding data in China are limited. METHODS: An observational analysis was performed in 26,305 STEMI patients, who were documented in China acute myocardial infarction (CAMI) Registry and treated in 162 hospitals from January 1st, 2013 to January 31th, 2016. We compared the differences such as demographic factors, social factors, medical history, risk factors, socioeconomic distribution and treatment strategies between EMS transport group and self-transport group. RESULTS: Only 4336 patients (16.5%) were transported by EMS. Patients with symptom onset outside, out-of-hospital cardiac arrest and presented to province-level hospital were more likely to use EMS. Besides those factors, low systolic blood pressure, severe dyspnea or syncope, and high Killip class were also positively related to EMS activation. Notably, compared to self-transport, use of EMS was associated with a shorter prehospital delay (median, 180 vs. 245 min, P < 0.0001) but similar door-to-needle time (median, 45 min vs. 52 min, P = 0.1400) and door-to-balloon time (median, 105 min vs. 103 min, P = 0.1834). CONCLUSIONS: EMS care for STEMI is greatly underused in China. EMS transport is associated with shorter onset-to-door time and higher rate of reperfusion, but not substantial reduction in treatment delays or mortality rate. Targeted efforts are needed to promote EMS use when chest pain occurs and to set up a unique regionalized STEMI network focusing on integration of prehospital care procedures in China. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01874691), retrospectively registered June 11, 2013.

The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. METHODS: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients' clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. RESULTS: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. CONCLUSIONS: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

Prognostic Significance of KIF-12 Functioning as a Tumour Suppressor in Papillary Thyroid Carcinoma.

Objective: To explore the potential value of a novel marker, KIF-12, in the progression and prognosis of papillary thyroid carcinoma (PTC) through integrative bioinformatics analysis, and clinical sample validation of the prognostic value of KIF-12. Materials and Methods: We extracted the clinicopathological data of 502 PTC patients from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset to identify reliable differentially expressed genes (DEGs) between high and low KIF12 expression groups. Functional enrichment analysis was performed on upregulated DEGs. Gene set enrichment analysis (GESA) was performed to identify the biological pathways. We further applied Cox analysis to determine independent risk factors associated with the PTC progression-free interval (PFI), and a nomogram was established to predict disease outcome. Finally, the prognostic value of KIF12 was validated by means of clinical samples from PTC patients with and without lateral lymph node metastasis. Results: On the basis of the TCGA-THCA database, we found that low KIF-12 expression was significantly related to a higher TNM stage (p<0.05), BRAF mutation status (p = 0.019), and extrathyroidal extension (p<0.001). KIF-12 was an independent prognostic factor of PTC (OR=0.319, 95% CI=0.130-0.784, P=0.013). The prognostic value of KIF12 was also successfully validated in clinical samples from twenty-nine PTC patients with lateral lymph node metastasis by comparison with twenty-two PTC patients without lymph node metastasis (P = 0.004). Conclusions: We report that KIF-12 has a tumor suppressive function in PTC and may be a useful prognostic tool to predict patient outcomes.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records.

OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies.

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.

Prognostic factors and clinical survival outcome in patients with primary mediastinal diffuse large B-cell lymphoma in rituximab era: A population-based study.

The goal of this study was to investigate the clinical characteristics, prognostic variables, and survival of patients with primary mediastinal diffuse large B cell lymphoma (PMBCL) in the rituximab era. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PMBCL patients diagnosed between 2000 and 2019. The Kaplan-Meier (K-M) technique and log-rank test were used to assess overall survival (OS) and disease-specific survival (DSS). The independent prognostic variables for OS and DSS were identified using univariate and multivariate Cox regression analysis. Nomograms were created to predict survival prospects according to identified prognostic indicators. Totally, 841 patients were enrolled with PMBCL. One-year, 5-year, and 10-year OS rates were 93.99%, 85.04%, and 81.76%, and the corresponding DSS rates were 95.27%, 87.37%, and 85.98%. The results of multivariate Cox regression analysis demonstrated that age, years of diagnosis, Ann arbor staging, and chemotherapy were independent prognostic factors for survival. Nomograms designed exclusively for PMBCL were created to forecast the likelihood of 1-year, 5-year, and 10-year OS and DSS, respectively. The Harrell concordance index (C-index) for the nomograms predictions of OS and DSS were 0.704 and 0.733, respectively, which showed the established model harboring powerful and accurate performance. The present study revealed that incidence of PMBCL has been consistently rising over the last 20 years. Simultaneously, survival rates have improved tremendously. Rituximab based immunochemotherapy has emerged as an effective treatment option, leading to enhanced OS and DSS outcomes. Furthermore, the nomograms specifically developed for PMBCL have demonstrated robustness and accuracy in forecasting OS and DSS rates at 1, 5, and 10 years. These predictive tools can be valuable for clinicians in accurately estimating prognosis and establishing personalized treatment plans and follow-up protocols.

Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

Metabolomics analysis of serum and urine in type 1 diabetes patients with different time in range derived from continuous glucose monitoring.

BACKGROUND: Time in range (TIR), as an important glycemic variability (GV) index, is clearly associated with disease complications in type 1 diabetes (T1D). Metabolic dysregulation is also involved in the risks of T1D complications. However, the relationship between metabolites and TIR remains poorly understood. We used metabolomics to investigate metabolic profile changes in T1D patients with different TIR. METHODS: This study included 85 T1D patients and 81 healthy controls. GV indices, including TIR, were collected from continuous glucose monitoring system. The patients were compared within two subgroups: TIR-L (TIR < 50%, n = 21) and TIR-H (TIR > 70%, n = 14). To screen for differentially abundant metabolites and metabolic pathways, serum and urine samples were obtained for untargeted metabolomics by ultra-performance liquid chromatography‒mass spectrometry. Correlation analysis was conducted with GV metrics and screened biomarkers. RESULTS: Metabolites were significantly altered in T1D and subgroups. Compared with healthy controls, T1D patients had higher serum levels of 5-hydroxy-L-tryptophan, 5-methoxyindoleacetate, 4-(2-aminophenyl)-2,4-dioxobutanoate, and 4-pyridoxic acid and higher urine levels of thromboxane B3 but lower urine levels of hypoxanthine. Compared with TIR-H group, The TIR-L subgroup had lower serum levels of 5-hydroxy-L-tryptophan and mevalonolactone and lower urine levels of thromboxane B3 and phenylbutyrylglutamine. Dysregulation of pathways, such as tryptophan, vitamin B6 and purine metabolism, may be involved in the mechanism of diabetic complications related to glycemic homeostasis. Mevalonolactone, hypoxanthine and phenylbutyrylglutamine showed close correlation with TIR. CONCLUSIONS: We identified altered metabolic profiles in T1D individuals with different TIR. These findings provide new insights and merit further exploration of the underlying molecular pathways relating to diabetic complications.

Visual detection of water content in liquor with near-infrared fluorescence sensor assisted by smartphone.

Water content was an essential indicator in organic solvents, and it was necessary to develop a facile, cheap and readily available tool for the real-time, specifical and sensitive detection of water content. In this work, two novel D-π-A type near-infrared fluorescence sensors (DCM-1 and DCM-2) were designed and synthesized for the detection of trace water in organic solvents. DCM-1 and DCM-2 with solvent-dependent effects and large Stokes shift (>120 nm) showed good linear "intensity-to-content" relationships in four commonly-used organic solvents, and accomplished the ultra-fast and high-accuracy detection of the trace water in organic solvents. More importantly, a portable, fast, and accurate smartphone-assisted visual assay was designed for visual quantitative detection of the water content in organic solvents with a detection limit as low as 1.028 % v/v (e.g. in ethanol) and a wide detection range (0-60 % v/v). The smartphone-based visual assay was further applied to estimate the water content in disinfection alcohol and commercial liquor, which furnished a new strategy and broad prospects to achieve the accurate onsite detection of water content.

Summary of the 2022 Report on Cardiovascular Health and Diseases in China.

ABSTRACT: Recent decades have seen the remarkable development of China in medical accessibility and quality index, and the application of a number of new advanced cardiovascular technologies benefits more patients. However, according to the Annual Report on Cardiovascular Health and Diseases in China published in this article, which was organized and summarized by National Center for Cardiovascular Diseases, there is still a huge population living with risk factors of cardiovascular diseases (CVD), and the morbidity and mortality of CVD are increasing. It is estimated that there are around 330 million patients suffering from CVD currently, including 245 million of hypertension, 13 million of stroke, 45.3 million of peripheral artery disease, 11.39 million of coronary heart disease (CHD), 8.9 million of heart failure, 5 million of pulmonary heart disease, 4.87 million of atrial fibrillation, 2.5 million of rheumatic heart disease, and 2 million of congenital heart disease. Tobacco use, diet and nutrition factors, physical activity, overweight and obesity, and psychological factors are what affect cardiovascular health, while hypertension, dyslipidemia, diabetes, chronic kidney disease, metabolic syndrome, and air pollution are the risk factors for CVD. In this article, in addition to risk factors for CVD, we also report the epidemiological trends of CVD, including CHD, cerebrovascular disease, arrhythmias, valvular heart disease, congenital heart disease, cardiomyopathy, heart failure, pulmonary vascular disease and venous thromboembolism, and aortic and peripheral artery diseases, as well as the basic research and medical device development in CVD. In a word, China has entered a new stage of transforming from high-speed development focusing on scale growth to high-quality development emphasizing on strategic and key technological development to curb the trend of increasing incidence and mortality of CVD.

Prediction of postoperative hypokalemia in patients with oral cancer undergoing en bloc cancer resection: a retrospective cohort study.

BACKGROUND: The factors associated with postoperative hypokalemia in patients with oral cancer remain unclear. We determined the preoperative factors associated with postoperative hypokalemia in patients with oral cancer following en bloc cancer resection and established a nomogram for postoperative hypokalemia prediction. METHODS: Data from 381 patients with oral cancer who underwent en bloc cancer resection were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the risk factors for postoperative hypokalemia. We used receiver operating characteristic (ROC) curves to quantify the factors' effectiveness. A nomogram was created to show each predictor's relative weight and the likelihood of postoperative hypokalemia development. The multinomial regression model's effectiveness was also evaluated. RESULTS: Preoperative factors, including sex, preoperative serum potassium level, and preoperative platelet-to-lymphocyte ratio (PLR), were significantly associated with postoperative hypokalemia. Based on the ROC curve, the preoperative serum potassium and PLR cut-off levels were 3.98 mmol/L and 117, respectively. Further multivariate analysis indicated that female sex, preoperative serum potassium level < 3.98 mmol/L, and preoperative PLR ≥ 117 were independently associated with postoperative hypokalemia. We constructed a predictive nomogram with all these factors for the risk of postoperative hypokalemia with good discrimination and internal validation. CONCLUSIONS: The predictive nomogram for postoperative hypokalemia risk constructed with these factors had good discrimination and internal validation. The developed nomogram will add value to these independent risk factors that can be identified at admission in order to predict postoperative hypokalemia.

Archaea are better adapted to antimony stress than their bacterial counterparts in Xikuangshan groundwater.

Archaea are important ecological components of microbial communities in various environments, but are currently poorly investigated in antimony (Sb) contaminated groundwater particularly on their ecological differences in comparison with bacteria. To address this issue, groundwater samples were collected from Xikuangshan aquifer along an Sb gradient and subjected to 16S rRNA gene amplicon sequencing and bioinformatic analysis. The results demonstrated that bacterial communities were more susceptibly affected by elevated Sb concentration than their archaeal counterparts, and the positive stimulation of Sb concentration on bacterial diversity coincided with the intermediate disturbance hypothesis. Overall, the balance of environmental variables (Sb, pH, and EC), competitive interactions, and stochastic events jointly regulated bacterial and archaeal communities. Linear fitting analysis revealed that Sb significantly drove the deterministic process (heterogeneous selection) of bacterial communities, whereas stochastic process (dispersal limitation) contributed more to archaeal community assembly. In contract, the assembly of Sb-resistant bacteria and archaea was dominated by the stochastic process (undominated), which implied the important role of diversification and drift instead of selection. Compared with Sb-resistant microorganisms, bacterial and archaeal communities showed lower niche width, which may result from the constraints of Sb concentration and competitive interaction. Moreover, Sb-resistant archaea had a higher niche than that of Sb-resistant bacteria via investing on flexible metabolic pathways such as organic metabolism, ammonia oxidation; and carbon fixation to enhance their competitiveness. Our results offered new insights into the ecological adaptation mechanisms of bacteria and archaea in Sb-contaminated groundwater.

Novel insights into the mechanisms for Sb mobilization in groundwater in a mining area: A colloid field study.

Colloids may play an important role in the geochemical cycle of antimony (Sb). However, the controlling behaviors of colloids on Sb fate in contaminated groundwater are not available. To investigate the effects of colloids on Sb mobility, groundwater samples from Xikuangshan Sb Mine's two main aquifers (the D3s2 aquifer and the D3x4 aquifer) were successively (ultra)filtered through progressively decreasing pore sizes (0.45 µm, 100 kDa, 50 kDa and 5 kDa). The results showed that 0.1-84.1% of Sb was adsorbed or carried by colloids, which corresponded to Sb concentration ranging between 0 and 2973 µg/L in the colloids (0.45 µm - 5 kDa). In both aquifers, Sb was closely associated with organic colloids (r = 0.72 p < 0.05 for the D3x4 aquifer, r = 0.94 p < 0.01 for the D3s2 aquifer). Parallel factor analysis of the three-dimensional fluorescence spectra determined that the protein-like substances in the D3x4 aquifer and the humus-like substances in the D3s2 aquifer controlled Sb behavior. X-ray absorption spectroscopy confirmed Sb complexing with organic substances. Competitive adsorption of As and Sb suppressed the complexation of colloids with Sb, particularly in the D3x4 aquifer (r = -0.71, p < 0.05). Sb mobility was also influenced by the redox of the groundwater system. As the oxidation-reduction potential and dissolved oxygen increased, Sb in the colloidal fractions decreased. These findings provide new insights into the mechanisms involved in Sb fate affected by colloids, establishing the theoretical basis for developing effective Sb and even metalloid pollution remediation strategies.

Spatial structure of the non-integrable discrete defocusing Hirota equation.

In this paper, we investigate the spatial property of the non-integrable discrete defocusing Hirota equation utilizing a planar nonlinear discrete dynamical map method. We construct the periodic orbit solutions of the stationary discrete defocusing Hirota equation. The behavior of the orbits in the vicinity of the special periodic solution is analyzed by taking advantage of the named residue. We characterize the effects of the parameters on the aperiodic orbits with the aid of numerical simulations. A comparison with the non-integrable discrete defocusing nonlinear Schrödinger equation case reveals that the non-integrable discrete defocusing Hirota equation has more abundant spatial properties. Rather an interesting and novel thing is that for any initial value, there exists triperiodic solutions for a reduced map.

Real-World Immunosuppressant Treatment Patterns for Patients with Lupus Nephritis in the United States.

INTRODUCTION: Lupus nephritis (LN) treatment aims to control and prevent flares and irreversible kidney damage. Around 30% of patients are unresponsive to treatment; however, real-world LN treatment patterns have not been reported. Objectives of this retrospective cohort study (GSK 209758) were to quantify the time to switching/re-initiating induction therapy in patients with LN initiating immunosuppressant therapy and conversion from induction to maintenance immunosuppressant therapy, and to assess corticosteroid use. METHODS: Patients with LN initiating induction or maintenance immunosuppressant therapy were identified using claims data. Patients were followed up from the index date (immunosuppressant initiation date) until treatment discontinuation, death, disenrollment, administrative censoring, or the end of follow-up period. The cumulative incidence of switching/re-initiating induction therapy and conversion to maintenance therapy was estimated using outpatient pharmacy claims and procedure codes. Corticosteroid use was estimated using pharmacy claims; a mean daily dose of ≥ 7.5 mg/day was considered high. RESULTS: In total, 5000 patients with LN contributed 5516 treatment episodes (induction cohort, N = 372; maintenance cohort, N = 5144). In the induction cohort, the cumulative incidence (95% confidence interval) of switching between induction therapies was 24.6% (20.1-30.0) at 12 months, while 59.6% (52.4-66.1) of patients converted to maintenance therapy at 12 months. In the maintenance cohort, 21.2% (19.9-22.5) re-initiated induction therapy at 12 months. Oral corticosteroid use decreased during the follow-up in both cohorts, but 21.5% of patients remained on a high dose at 12 months in the induction cohort, while 15.8% in the maintenance cohort were taking a high dose at 24 months. CONCLUSIONS: Around a quarter of patients with LN initiating immunosuppressant therapy switched within 12 months, while a fifth re-initiated induction therapy within 12 months. Use of high corticosteroid doses were observed during 24 months of follow-up. These data suggest that many patients do not respond to existing standard LN therapies.

Comparative genomics reveals intraspecific divergence of Acidithiobacillus ferrooxidans: insights from evolutionary adaptation.

Acidithiobacillus ferrooxidans serves as a model chemolithoautotrophic organism in extremely acidic environments, which has attracted much attention due to its unique metabolism and strong adaptability. However, little was known about the divergences along the evolutionary process based on whole genomes. Herein, we isolated six strains of A. ferrooxidans from mining areas in China and Zambia, and used comparative genomics to investigate the intra-species divergences. The results indicated that A. ferrooxidans diverged into three groups from a common ancestor, and the pan-genome is 'open'. The ancestral reconstruction of A. ferrooxidans indicated that genome sizes experienced a trend of increase in the very earliest days before a decreasing tendency during the evolutionary process, suggesting that both gene gain and gene loss played crucial roles in A. ferrooxidans genome flexibility. Meanwhile, 23 single-copy orthologous groups (OGs) were under positive selection. The differences of rusticyanin (Rus) sequences (the key protein in the iron oxidation pathway) and type IV secretion system (T4SS) composition in the A. ferrooxidans were both related to their group divergences, which contributed to their intraspecific diversity. This study improved our understanding of the divergent evolution and environmental adaptation of A. ferrooxidans at the genome level in extreme conditions, which provided theoretical support for the survival mechanism of living creatures at the extreme.

BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52-0.94, P = 0.02], lower RR (0.49, 95% CI, 0.31-0.76, P = 0.002), higher mucositis (3.43, 95% CI, 2.29-5.16, P = 0.001), renal toxicity (4.49, 95% CI, 2.68-7.51, P = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03-3.40, P = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD -0.64, 95% CI, -1.46 to 0.18, P = 0.13), PE (pooled WMD -0.3, 95% CI, -1.68 to 2.28, P = 0.77), OS (0.73, 95% CI, 0.52-1.01, P = 0.07), and NRM (1.51, 95% CI, 0.76-2.98, P = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.

Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.

BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. METHODS: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. RESULTS: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. CONCLUSIONS: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

Qualitative and quantitative superb vascular imaging in the diagnosis of thyroid nodules ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4).

Background: To compare qualitative and quantitative superb microvascular imaging (SMI) and determine the value of SMI in the diagnosis of thyroid nodules (TNs) ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4). Methods: From October 2020 to June 2022, 106 patients with 109 C-TIRADS 4 (C-TR4) TNs (81 malignant, 28 benign) at the Peking Union Medical College Hospital were included. Qualitative SMI reflected the vascular pattern of the TNs and quantitative SMI was recorded by the vascular index (VI) of the nodules. Results: The VI was significantly higher in malignant nodules versus benign nodules both in the longitudinal (19.9±11.4 vs. 13.8±10.6, P=0.01) and transverse (20.2±12.1 vs. 11.3±8.7, P=0.001) sections. The area under the curve (AUC) of qualitative and quantitative SMI did not show a statistical difference in the longitudinal {0.657 [95% confidence interval (CI): 0.560-0.745] vs. 0.646 (95% CI: 0.549-0.735), P=0.79} and transverse [0.696 (95% CI: 0.600-0.780) vs. 0.725 (95% CI: 0.632-0.806), P=0.51] sections. Next, we combined qualitative and quantitative SMI to upgrade and downgrade the C-TIRADS classification. If a C-TR4B nodule had VIsum >12.2 or intra-nodular vascularity, the original C-TIRADS was upgraded to C-TR4C. If a C-TR4C or C-TR4B nodule manifested VIsum ≤12.2 and no intra-nodular vascularity, the original C-TIRADS was downgraded to C-TR4A. As a result, 18 C-TR4C nodules were downgraded to C-TR4A and 14 C-TR4B nodules were upgraded to C-TR4C. The new model of SMI + C-TIRADS showed high sensitivity (93.8%) and accuracy (79.8%). Conclusions: There is no statistical difference between qualitative and quantitative SMI in the diagnosis of C-TR4 TNs. The combination of qualitative and quantitative SMI may have the potential to manage diagnosis of C-TR4 nodules.