Oxidative DNA damage in reconstituting T cells is associated with relapse and inferior survival after allo-SCT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment option for a number of hematologic malignancies. Its therapeutic potential relies on the potency of donor T cells to eliminate residual malignant cells, the so-called graft-versus-leukemia (GVL) effect. Disease relapse remains the most frequent treatment failure and is associated with poor outcome. Therefore, it is inevitable to decipher mechanisms that weaken GVL. In recent years, studies of tumor biology have revealed that metabolic remodeling of the micromilieu can critically regulate immune responses. Accumulation of reactive oxygen species leads to a metabolic condition known as oxidative stress, which can severely hamper T cells. Currently, only a few studies, mainly using preclinical models, have demonstrated the occurrence of oxidative stress after allo-SCTs. Therefore, we sought to investigate oxidative stress in a well-characterized group of patients who underwent allo-SCT and its impact on reconstituting T cells. We identified high concentrations of serum 8-hydroxydeoxyguanosine (8-OHdG) as an established biomarker for oxidative stress. 8-OHdG is one of the major products of DNA oxidation, which is normally rapidly removed. After allo-SCT, T cells accumulated oxidative DNA damage. High cellular 8-OHdG content (8-OHdGhi) was associated not only with signs of enhanced T-cell activation but also premature exhaustion. The inability of 8-OHdGhi T cells to efficiently target malignant cells or produce cytotoxic granzyme B and interferon gamma was associated with a significantly increased relapse risk and a shorter overall survival. Taken together, our novel findings could give reason to focus on bolstering DNA repair in reconstituting T cells as a means to improve GVL efficacy.

[The ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion].

Objective: The present retrospective study aimed to analyses the ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion. Methods: A total of 37 advanced aged patients diagnosed with atrial fibrillation(>65 years)who underwent left atrial appendage occlusion (LAAO) in Xuanwu Hospital of Capital Medical University from March 2021 to March 2022 were enrolled in this study. All patients received supplemental oxygen by a new nasopharyngeal airway to ensure intraoperative ventilation. The primary outcome was the occurrence of hypoxemia. The secondary outcomes included the incidence of hypotension after anesthesia, the incidence of body movement during surgery, significant fluctuations of the vital signs such as mean arterial pressure (MAP), heart rate (HR), saturation of pulse oxygen (SpO2) and respiratory rate (RR) at different time points (T1: pre-operation; T2: at the time of placing nasopharyngeal airway; T3: at the time of placing transesophageal echocardiography(TEE); T4: at the time of TEE intraoperative exploration; T5: end of the surgery; T6: at the time of patient woke up), and the incidence of postoperative adverse events. Results: There were 24 males and 13 females with a mean age of (73.8±7.7) years. The incidence of hypoxemia was 16.2% (6/37), which could return to normal after simple treatment. The incidence of hypotension was 27.0% (10/37), occurred after anesthesia induction mainly.32.4% (12/37) of the patients experienced movements, but no adverse events led to surgical termination. MAP at different time points was significantly different (P=0.001), but other vital signs of HR, SpO2 and RR were not significantly different(all P>0.05), without serious hemodynamic fluctuations. The incidence of postoperative adverse cardiovascular events was 10.8% (4/37), and delirium was 2.7% (1/37). All patients successfully completed the surgery and were safely discharged from the hospital. Conclusion: The new nasopharyngeal airway can meet the requirements of airway management during left atrial appendage occlusion under intravenous anesthesia without serious adverse events.

[Analysis of clinical characteristics of 129 acute and chronic occupational brucellosis in HulunBuir City].

Objective: To analyze the epidemiological characteristics and clinical data of acute and chronic occupational brucellosis patients in order to provide a scientific basis for the prevention and treatment of occupational brucellosis. Methods: In October 2022, a study was conducted on 129 patients diagnosed with occupational brucellosis by HulunBuir Center for Disease Control and Prevention from January 2016 to December 2021. The epidemiological characteristics, clinical features, and laboratory test results of patients in the acute and chronic phases were compared and analyzed using chi-square test and student's t test. Results: The acute phase patients included 38 men and 4 women with an average age of (36.6±8.4) years old; the chronic phase patients included 73 men and 14 women with an average age of (38.4±7.9) years old. There were no significant differences in gender and age between the two groups (P>0.05). The patients had a clear history of occupational exposure, and the proportion of veterinarians in acute stage (21 cases, 50.0%) was significantly higher than that in chronic stage (25 cases, 28.7%), the difference was statistically significant (P<0.05). The symptoms of fever and loss of appetite in acute phase of occupational brucellosis were significantly higher than those in chronic phase, and the symptoms of fatigue and joint muscle pain were significantly lower than those in chronic phase, with statistical significances (P<0.05). The increase of alanine aminotransferase, aspartate aminotransferase, C-reactive protein, erythrocyte sedimentation rate and positive rate of blood culture in acute stage were significantly higher than those in chronic stage, with statistical significances (P<0.05) . Conclusion: Occupational brucellosis patients are predominantly middle-aged men, the acute phase is characterized by fever, loss of appetite, and increased inflammatory indicators and liver enzymes, while the chronic phase is characterized by symptoms such as fatigue and joint muscle pain. Brucellosis related occupational exposure population should seek medical treatment as soon as possible when the above symptoms occur, timely detection and treatment of occupational diseases.

A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus-Associated Tuberculous Meningitis: The LASER-TBM Trial.

BACKGROUND: Drug regimens that include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in tuberculous meningitis (TBM). Safety data on their use in combination and in the context of human immunodeficiency virus (HIV) are needed to inform clinical trial design. METHODS: We conducted a phase 2, open-label, parallel-design, randomized, controlled trial to assess the safety of high-dose rifampicin, linezolid, and high-dose aspirin in HIV-associated TBM. Participants were randomized (1.4:1:1) to 3 treatment arms (1, standard of care [SOC]; 2, SOC + additional rifampicin [up to 35 mg/kg/d] + linezolid 1200 mg/d reducing after 28 days to 600 mg/d; 3, as per arm 2 + aspirin 1000 mg/d) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed. RESULTS: A total of 52 participants with HIV-associated TBM were randomized; 59% had mild disease (British Medical Research Council (MRC) grade 1) vs 39% (grade 2) vs 2% (grade 3). AESI or death occurred in 10 of 16 (63%; arm 3) vs 4 of 14 (29%; arm 2) vs 6 of 20 (30%; arm 1; P = .083). The cumulative proportion of AESI or death (Kaplan-Meier) demonstrated worse outcomes in arm 3 vs arm 1 (P = .04); however, only 1 event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) between arms. CONCLUSIONS: High-dose rifampicin and adjunctive linezolid can safely be added to the standard of care in HIV-associated TBM. Larger studies are required to determine whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit. CLINICAL TRIALS REGISTRATION: NCT03927313.

Lamellar Fluctuations Melt Ferroelectricity.

We consider a standard Ginzburg-Landau model of a ferroelectric whose electrical polarization is coupled to gradients of elastic strain. At the harmonic level, such flexoelectric interaction is known to hybridize acoustic and optic phonon modes and lead to phases with modulated lattice structures that precede the state with spontaneously broken inversion symmetry. Here, we use the self-consistent phonon approximation to calculate the effects of thermal and quantum polarization fluctuations on the bare hybridized modes to show that such long-range modulated order is unstable at all temperatures. We discuss the implications for the nearly ferroelectric SrTiO_{3} and KTaO_{3}, and we propose that these systems are melted versions of an underlying modulated state that is dominated by nonzero momentum thermal fluctuations except at the very lowest temperatures.

Effect of artesunate on cardiovascular complications in periodontitis in a type I diabetes rat model and related mechanisms.

PURPOSE: Both cardiovascular disease and periodontitis are complications of diabetes that have a great impact on human life and health. Our previous research found that artesunate can effectively improve cardiovascular disease in diabetes and has an inhibitory effect on periodontal disease. Therefore, the present study aimed to explore the potential therapeutic possibility of artesunate in the protection against cardiovascular complications in periodontitis with type I diabetes rats and to elucidate the possible underlying mechanisms. METHODS: Sprague‒Dawley rats were randomly divided into the healthy, diabetic, periodontitis, diabetic with periodontitis, and artesunate treatment groups (10, 30, and 60 mg/kg, i.g.). After artesunate treatment, oral swabs were collected and used to determine changes in the oral flora. Micro-CT was performed to observe changes in alveolar bone. Blood samples were processed to measure various parameters, while cardiovascular tissues were evaluated by haematoxylin-eosin, Masson, Sirius red, and TUNEL staining to observe fibrosis and apoptosis. The protein and mRNA expression levels in the alveolar bone and cardiovascular tissues were detected using immunohistochemistry and RT‒PCR. RESULTS: Diabetic rats with periodontitis and cardiovascular complications maintained heart and body weight but exhibited reduced blood glucose levels, and they were able to regulate blood lipid indicators at normal levels after artesunate treatment. The staining assays suggested that treatment with 60 mg/kg artesunate has a significant therapeutic effect on myocardial apoptotic fibrosis. The high expression of NF-κB, TLR4, VEGF, ICAM-1, p38 MAPK, TGF-ß, Smad2, and MMP9 in the alveolar bone and cardiovascular tissue in the type I diabetes and type I diabetes with periodontitis rat models was reduced after treatment with artesunate in a concentration-dependent manner. Micro-CT showed that treatment with 60 mg/kg artesunate effectively alleviated alveolar bone resorption and density reduction. The sequencing results suggested that each model group of rats had vascular and oral flora dysbiosis, but artesunate treatment could correct the dysbacteriosis. CONCLUSIONS: Periodontitis-related pathogenic bacteria cause dysbiosis of the oral and intravascular flora in type I diabetes and aggravate cardiovascular complications. The mechanism by which periodontitis aggravates cardiovascular complications involves the NF-κB pathway, which induces myocardial apoptosis, fibrosis, and vascular inflammation.

A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.

BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

[Annual progress on molecular biological diagnosis of tuberculosis 2022].

Tuberculosis (TB) continues to be a global public health issue that threatens human health, and rapid and accurate pathogen detection is the key to early diagnosis and effective treatment. In recent years, the pathogenic diagnosis of tuberculosis is expanding from traditional bacteriological diagnosis to molecular diagnosis. In the past year, Xper MTB/RIF Ultra technology with good diagnostic performance has been applied more often to the detection of non-respiratory samples, and Xpert XDR and second-generation linear probe technology provided more basis for early and accurate diagnosis of multidrug resistance; genome sequencing technology has also been developed and applied more often to the detection of non-culture sample detection, and the cost and time required for detection have been relatively reduced. Truenat technology, which is more suitable for primary care centers, is more widely used; new TB detection technologies, such as cell-free DNA testing and mass spectrometry, are also being developed and are expected to become important tools for early and rapid diagnosis of TB and drug-resistant TB. In this review, we synthesized the major research results of molecular biology diagnosis of tuberculosis around the world from 1st October 2021 to 30th September 2022, and comprehensively evaluated the advantages, disadvantages and current application of molecular biology detection technologies to provide a significant basis for clinical decision-making.

[Evaluation of the efficacy of tenofovir disoproxil fumarate in the treatment of chronic hepatitis B combined with nonalcoholic fatty liver disease by high-sensitivity detection of HBV DNA levels].

Objective: To observe the efficacy of tenofovir disoproxil fumarate (TDF) antiviral therapy in patients with chronic hepatitis B (CHB) combined with nonalcoholic fatty liver disease (NAFLD), so as to provide evidence-based evidence in these special populations. Methods: Data from 91 CHB cases who received TDF 300 mg/d antiviral therapy for 96 weeks were analyzed retrospectively. Among them, 43 cases with NAFLD were included in the study group, and 48 cases without NAFLD were included in the control group. The virological and biochemical responses of the two groups of patients at 12, 24, 48, and 96 weeks were compared. Among them, 69 patients underwent highly sensitive detection of HBV DNA. The t-test and χ (2) test were performed on the data. Results: ALT normalization rate was lower in the study group (42%, 51%) at 12 and 24 weeks of treatment than that in the control group (69%, 79%), and the difference was statistically significant (P < 0.05). However, there was no statistically significant difference between the two groups at 48 and 96 weeks. HBV DNA concentration below the lower limit of detection (200 IU/ml) was lower in the study group at 12 weeks of treatment than in the control group (35% vs. 56%), and the difference was statistically significant (P < 0.05). However, there was no statistically significant difference between the two groups at 24, 48, and 96 weeks. Furthermore, HBV DNA concentration below the lower limit was significantly lower in the study group than that in the control group at 12, 24, 48, and 96 weeks of treatment when the lower limit of HBV DNA detection was set at 20IU/ml, and the difference was statistically significant (P < 0.05). The HBeAg serological negative conversion rate was gradually higher in the study group at 48 and 96 weeks of treatment than in the control group, and the difference was not statistically significant. Conclusion: TDF antiviral treatment can affect the virological and biochemical responses of NAFLD in chronic hepatitis B.

[Epidemiological characteristics of familiar adult inherited metabolic liver disease].

Inherited metabolic liver diseases can occur in multi-age groups such as children, adolescents, adults, and others. With the improvement of diagnosis and treatment levels, more and more patients with childhood-onset diseases are surviving into adulthood. Some diseases originally faced by pediatric hepatologists also appear in adult hepatology clinics. This raises new challenges for adult hepatologists, requiring them to master more professional knowledge. However, specific data on the incidence rate of most inherited metabolic liver diseases is still lacking in our country. This article reviews the research progress of hereditary metabolic liver diseases and summarizes the epidemiological characteristics of familiar hereditary metabolic liver diseases in China.

[Application of transbronchial cryobiopsy in the diagnosis of postoperative complications after lung transplantation: a report of 6 cases].

Objective: To investigate the efficacy and safety of transbronchial cryobiopsy (TBCB) after lung transplantation. Methods: The clinical characteristics, TBCB procedure, diagnosis and treatment, and outcomes of lung transplant recipients of 6 patients (all male, aged 33-67 years) with TBCB in China-Japan Friendship Hospital from May to November 2021 were retrospectively analyzed. Results: Among the 6 patients diagnosed by TBCB, there were 2 cases of organizing pneumonia, 1 acute cellular rejection, 1 antibody-mediated rejection, and 1 bronchiolitis obliterans, and 1 diffuse alveolar damage. After the clinical diagnosis was confirmed, the condition improved after adjustment of the treatments followed. There were no serious complications related to the TBCB procedure. Conclusion: TBCB is valuable and relatively safe in the diagnosis of complications after lung transplantation, but the indications need to be strictly controlled.

[A study on the mediation effect of insulin use on diabetic retinopathy in a community population].

Objective: To explore the risk factors for diabetic retinopathy (DR) in patients with diabetes and the mediating effect of insulin use on the relationship between glycated hemoglobin (HbA1c) and DR. Methods: Cross-sectional study. Random cluster sampling was conducted using a random number table method. A total of 84 sampling points (including 2 pilot points) were selected from the registered population of patients with type 2 diabetes aged 50 years and above at the Disease Prevention and Control Center in Funing County, Jiangsu Province. Questionnaires and biochemical tests were performed to obtain information on the general characteristics of the participants, medical history, insulin use, and glycated hemoglobin (HbA1c) levels. Ocular examinations, including anterior segment and fundus examinations, were conducted. The participants were divided into two groups, DR (diabetic retinopathy) and non-DR, based on the presence or absence of retinal hemorrhages, hard exudates, cotton wool spots, neovascularization, preretinal or vitreous hemorrhage. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors for DR. The Karlson-Holm-Breen analysis method was used for mediation effect analysis. Results: A total of 2 067 diabetic patients were enrolled, of whom 1 965 completed the survey and 1 802 were included in the statistical analysis, resulting in a response rate of 87.2%. Among them, 660 patients were diagnosed with DR, with a detection rate of 36.63%. The results of multivariate analysis showed that diabetes duration (OR=1.166, 95%CI: 1.138-1.196), family history of diabetes (OR=1.325, 95%CI: 1.001-1.755), insulin therapy (OR=1.995, 95%CI: 1.434-2.777), HbA1c level (OR=1.513, 95%CI: 1.189-1.925), and alcohol consumption (OR=0.712, 95%CI: 0.514-0.985) were independent risk factors for DR. The mediating effect of insulin use accounted for 13.67% of the total effect of HbA1c on DR (P<0.001). Conclusions: The risk factors for DR in patients with diabetes include a history of insulin therapy, longer duration of diabetes, family history of diabetes, alcohol consumption, and high HbA1c levels. Insulin use increases the impact of HbA1c on DR and has a partial mediating effect on DR.

[Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation].

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

Cohesive properties of PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces.

First principles calculations reveal that the effects of PbBi on the cohesive properties of Fe3O4 and (Fe,Cr)3O4: PbBi can reduce the cohesive strength of the oxides, and the contents of O and Cr on the O-terminated oxide side play a significant role in the cohesive properties of the PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces. Specifically, the performance of oxidation decreases more significantly under the conditions of insufficient oxygen, and a high ratio of Cr of the subsurface of oxides can lead to the reduction of the cohesive properties of O-terminated interfaces. Calculations also show that the Pb-O-terminated interfaces are energetically favorable and are more stable than the Bi-O-terminated surfaces due to the strong bond of Pb-O, while the Bi-Cr and Bi-Fe interfaces are more stable than the Pb-Cr and Pb-Fe interfaces. Moreover, it is found that the stability and cohesion of the PbBi/Fe3O4 and PbBi/(Fe,Cr)3O4 interfaces will decrease when the oxygen concentration is insufficient or the degree of wetting of PbBi of oxides is low, and the PbBi/Fe3O4 interface is more sensitive to these conditions. The bond-dissociation energies and electronic structures provide a deep understanding of various interface properties, and the obtained results are in good agreement with experimental measurements in the literature.

[Survival analysis of unexpected small cell lung cancer following surgery].

Objective: To investigate the survival and influencing factors of unexpected small cell lung cancer following surgery. Methods: We respectively reviewed the clinical characters of 104 patients who underwent surgical treatment and be proved as small cell lung cancer by pathology between January 2000 to October 2020 in Chinese PLA General Hospital. Overall survival (OS) of patients was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Results: Of 104 patients, 27 cases showed central lesions, and other 77 showed peripheral nodules. The margin of nodules was smooth in 42 cases on CT imaging. The median OS was 34.3 months and 5-year OS rate was 45.8%. Postoperative 5-year OS rates for patients were 52.1%, 45.4%, and 27.8% for clinical stages Ⅰ, Ⅱ, and Ⅲ, respectively. Univariate analyses identified the age, surgical access, surgical approach, N stage, TNM stage and vascular cancer emboli were associated with OS (P<0.05). The N stage was an independent factor for the OS of patients (P<0.05). Conclusions: Patients with unexpected SCLC, including Ⅰ, Ⅱ and part ⅢA stage have favorable outcome and can benefit from surgery and systemic postoperative treatment. Standard lobectomy plus systemic lymph node dissection is commended.

[Promoting the application of federated learning in medical imaging artificial intelligence].

Medical image-based artificial intelligence (AI) systems have shown great potential in assisting disease diagnosis and treatment. However, the challenges, such as data silos, privacy security and standardization, seriously impedes the application of AI in disease diagnosis and treatment. By integrating federated learning technology and FAIR data principle, it is possible to resolve the aforementioned obstacles. Then, it is able to maximize the value of multicenter data to develop a more efficient and accurate disease diagnosis and treatment AI systems, and promote the clinical application of medical image-based AI systems in the field of disease diagnosis and treatment.

[The stability and repeatability of radiomics features based on lung diffusion-weighted imaging].

Objective: To evaluate the feasibility, robustness and reproducibility of radiomics features derived from lung diffusion-weighted imaging (DWI). Methods: Thirty patients with pulmonary nodules/masses who underwent magnetic resonance imaging examination in the Department of Radiology, the First Affiliated Hospital of Guangzhou Medical University, from January 4 2019 to May 5 2019, including 16 males and 14 females, aged from 27 to 69 (57±11) years, were prospectively collected. Planar echo imaging (EPI) -DWI and fast spin-echo (TSE) -DWI scans were performed under free-breathing conditions. Each scan was repeated at an interval of 5 minutes, and the corresponding apparent diffusion coefficient (ADC) maps were reconstructed. Each DWI and ADC sequence (a total of eight groups of images) were manually segmented by two radiologists, and a total of 396 radiomics features in 6 categories were extracted from each group of images. Consistency correlation coefficient (CCC) and dynamic range (DR) were used to evaluate the robustness of features between two scans, and stable features were defined as both CCC values and DR values ≥0.85. Intra-observer and interobserver reproducibility were evaluated by intra-group correlation coefficient (ICC), and ICC values≥0.75 was considered to be good reproducibility. Results: Regardless of EPI or TSE technique, the number of robust features extracted fromDWI (TSE: n=197, EPI: n=169) were higher than that of the corresponding ADC (TSE: n=126, EPI: n=148). The proportion of robust features of TSE-DWI、EPI-DWI、TSE-ADC、EPI-ADC was 49.7% (197/396), 42.7% (169/396), 31.8% (126/396) and 37.4% (148/396), respectively. Of the 396 features, 54 (13.6%) of them demonstrated great robustness (CCC and DR≥0.85) and interobserver and interobserver reproducibility (ICC≥0.75) across all sequences. Conclusions: Radiomics features derived from lung DWI showed robustness and reproducibility. Different sequences and different feature clusters have different proportions of stable features, and some features have good robustness and reproducibility between different scans, different observers, and even different sequences.

[Value of radiomics model based on dynamic contrast-enhanced magnetic resonance imaging in differentiation fat-poor angiomyolipoma from alpha-fetoprotein-negative hepatocellular carcinoma in the background of non-cirrhotic liver].

Objective: To explore the value of radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (MRI) in differentiation fat-poor angiomyolipoma (fp-AML) from alpha-fetoprotein-negative hepatocellular carcinoma (n-HCC) in the background of non-cirrhotic liver. Methods: The complete data of 121 patients from Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University and Sun Yat-sen University Cancer Center with hepatic fp-AML and n-HCC confirmed by pathology from October 2010 to July 2020 were retrospectively analyzed. Among them, 75 were males and 46 were females, aged from 23 to 80 (55±12) years. A total of 93 patients from Zhongshan Hospital Affiliated to Fudan University were divided into the training cohort (n=75) and internal test cohort (n=18) according to entry time, and the patients of other 2 hospitals were divided into external test cohort (n=28). The radiomics features were extracted from the preoperative triple-phase contrast-enhanced images. The feature selection algorithm based on Joint Mutual Information Maximisation (JMIM) was used to extract the optimal feature subset, and support vector machine (SVM) was used to build the radiomics model. The diagnostic performance of radiomics model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with that of two radiologists. Results: In the internal cohort, the area under the curve (AUC) for the differential diagnosis between fp-AML and n-HCC of the radiomics model was 0.819 (with an accuracy of 72.2%), outperforming than radiologist 1 with 10 years of diagnostic experience (AUC=0.542, P=0.029) and radiologist 2 with 2 years of diagnostic experience (AUC=0.375, P=0.004). In the external cohort, the AUC of the radiomics model was 0.772 (with and accuracy of 71.4%), which was comparable to that of radiologist 1 (AUC=0.661, P=0.442) and better than that of radiologist 2 (AUC=0.400, P=0.008). Conclusion: The radiomics model based on dynamic contrast-enhanced MRI is of high accuracy for preoperatively differentiating hepatic fp-AML from n-HCC in the noncirrhotic liver.

[Characteristics and risk factors of spinal epidural hematoma after unilateral biportal endoscopic lumbar interbody fusion].

Objective: To investigate the incidence, characteristics and risk factors of spinal epidural hematoma after unilateral biportal endoscopic (UBE) lumbar spine surgery. Methods: The clinical data of 105 patients who underwent lumbar spine surgery under UBE in Guangdong Provincial People's Hospital from February 2020 to March 2021 were retrospectively reviewed. Of the patients, 48(45.7%) were male and 57(54.3%) were female, the mean age was (60.1±11.4) years (ranged 26 to 85 years). The MRI images at the third day post-surgery were observed, and the occurrence of hematoma was counted. Patients were assigned to normal group and hematoma group based on the presence of hematoma or not. The related clinical indicators of each patients were collected and used for comparison between two different groups. Logistic stepwise regression model was used to analyze whether each index was a risk factor for hematoma after the UBE lumbar fusion. Results: The total hematoma incidence rate was 28.6%(30/105), the symptomatic hematoma rate was 6.7%(7/105), and the hematoma reoperation rate was 0.9%(1/105). Univariate logistic regression analysis showed that hypertension (OR=3.368, 95%CI: 1.389-8.171), diabetes (OR=3.589, 95%CI: 1.230-10.476), admission systolic blood pressure>140 mmHg (1 mmHg=0.133 kPa,OR=3.687, 95%CI: 1.493-9.017), platelets<200×109/L (OR=0.300, 95%CI: 0.119-0.785), preoperative blood calcium<2.25 mmol/L (OR=0.340, 95%CI: 0.142-0.818), spinal stenosis grade D (OR=4.462, 95%CI: 1.810-10.996) were possible risk factors for spinal hematoma after UBE lumbar fusion. Multivariate logistic regression analysis showed that admission blood pressure systolic blood pressure>140 mmHg (OR=3.788, 95%CI:1.055-13.606), preoperative blood calcium<2.25 mmol/L (OR=78.544, 95%CI:3.895-1 584.058) and spinal stenosis grade D (OR=3.698, 95%CI:1.110-12.325) were risk factors for spinal hematoma after UBE lumbar fusion (all P<0.05). Conclusion: The types of spinal canal hematoma after UBE lumbar fusion include localized and extended type. The risk factors for hematoma include high systolic blood pressure on admission, low preoperative blood calcium and severe spinal stenosis.