NMR Immunosensor Based on a Targeted Gadolinium Nanoprobe for Detecting Salmonella in Milk.

Detecting harmful pathogens in food is not only a crucial aspect of food quality management but also an effective way to ensure public health. In this paper, a complete nuclear magnetic resonance biosensor based on a novel gadolinium (Gd)-targeting molecular probe was developed for the detection of Salmonella in milk. First, streptavidin was conjugated to the activated macromolecular polyaspartic acid (PASP) via an amide reaction to generate SA-PASP. Subsequently, the strong chelating and adsorption properties of PASP toward the lanthanide metal gadolinium ions were exploited to generate the magnetic complex (SA-PASP-Gd). Finally, the magnetic complex was linked to biotinylated antibodies to obtain the bioprobe and achieve the capture of Salmonella. Under optimal experimental conditions, the sensor we have constructed can achieve a rapid detection of Salmonella within 1.5 h, with a detection limit of 7.1 × 103 cfu mL-1.

New Advances in the Use of 18F-FET PET in the Diagnosis and Management of Adult High-Grade Gliomas / 罕见病研究

Gliomas are the most common primary intracranial tumors in adults, among which high-grade glioma patients are characterized by short survival and poor prognosis. The diagnosis, treatment, evaluation of effective treatments, and prognosis prediction of high-grade gliomas are of great significance for improving patient survival. Conventional enhanced magnetic resonance imaging has deficiencies in delineating tumor extent, identifying tumor progression and treatment-related changes. Therefore, there is a broad consensus to incorporate amino acid PET, and 18F-FET PET inparticular, into the diagnostic and therapeutic process of high-grade gliomas. In this article, we review the new research progress of 18F-FET PET in the diagnosis and treatment of adult high-grade glioma in recent years.

Rapid adaptive and acute stimulatory responses to low salinity stress in Pacific white shrimp (Litopenaeus vannamei): Insights from integrative transcriptomic and proteomic analysis.

The Pacific white shrimp (Litopenaeus vannamei) is a euryhaline crustacean capable of tolerating a wide range of ambient salinity, but the strategies of hepatopancreas to rapid adaptive or acute stimulatory responses to extremely low salinity fluctuations remains unclear. In this study, we integrated transcriptomic and proteomic analyses on the hepatopancreas derived from rapid adaptative (RA) and acute stimulatory (AS) responses to extremely low salinity stress (0.3 ppt) to unveil specific regulatory mechanisms. The RA group displayed normal epithelial cells and tubule structures, while the AS group showed histological changes and lesions. A total of 754 and 649 differentially expressed genes (DEGs) were identified in RA and AS treatments, respectively. For proteome, a total of 206 and 66 differentially expressed proteins (DEPs) were obtained in the RA/CT and AS/CT comparison groups, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted among the DEGs and DEPs, revealing that metabolic related pathways were significantly enriched pathways in both comparison groups. In addition, correlation analysis of transcriptomic and proteomic results showed that 20 and 3 pairs of DEGs/DEPs were identified in RA vs. CT and AS vs. CT comparison groups, respectively. This study is the first report on the rapid adaptive and acute stimulatory transcriptomic and proteomic responses of L. vannamei to extremely low salinity, shedding light on the mechanisms underlying osmoregulation in euryhaline crustaceans.

TRAF Family Member 4 Promotes Cardiac Hypertrophy Through the Activation of the AKT Pathway.

Background Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis of cardiac hypertrophy has led to a lack of development and application of therapeutic methods. Methods and Results Our study provides the first evidence that TRAF4, a member of the tumor necrosis factor receptor-associated factor (TRAF) family, acts as a promoter of cardiac hypertrophy. Here, Western blotting assays demonstrated that TRAF4 is upregulated in cardiac hypertrophy. Additionally, TRAF4 deletion inhibits the development of cardiac hypertrophy in a mouse model after transverse aortic constriction surgery, whereas its overexpression promotes phenylephrine stimulation-induced cardiomyocyte hypertrophy in primary neonatal rat cardiomyocytes. Mechanistically, RNA-seq analysis revealed that TRAF4 promoted the activation of the protein kinase B pathway during cardiac hypertrophy. Moreover, we found that inhibition of protein kinase B phosphorylation rescued the aggravated cardiomyocyte hypertrophic phenotypes caused by TRAF4 overexpression in phenylephrine-treated neonatal rat cardiomyocytes, suggesting that TRAF4 may regulate cardiac hypertrophy in a protein kinase B-dependent manner. Conclusions Our results revealed the regulatory function of TRAF4 in cardiac hypertrophy, which may provide new insights into developing therapeutic and preventive targets for this disease.

Metabolic dysfunction-associated fatty liver disease increased the risk of subclinical carotid atherosclerosis in China.

Background and aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to substitute NAFLD in 2020. This new term highlights the systematic metabolic disturbances that accompany fatty liver. We evaluated the correlations between MAFLD and subclinical carotid atherosclerosis (SCA) based on a nationwide health examination population in China. Methods: We performed a nationwide cross-sectional population and a Beijing retrospective cohort from 2009 to 2017. SCA was defined as elevated carotid intima-media thickness. The multivariable logistic and Cox models were used to analyze the association between MAFLD and SCA. Results: 153,482 participants were included in the cross-sectional study. MAFLD was significantly associated with SCA in fully adjusted models, with an odds ratio of 1.66; 95% confidence interval (CI): 1.62-1.70. This association was consistent in the cohort, with a hazard ratio (HR) of 1.31. The association between baseline MAFLD and incident SCA increased with hepatic steatosis severity. Subgroup analysis showed an interaction between age and MAFLD, with a higher risk in younger groups (HR:1.67, 95% CI: 1.17-2.40). Conclusion: In this large cross-section and cohort study, MAFLD was significantly associated with the presence and development of SCA. Further, the risk was higher among MAFLD individuals with high hepatic steatosis index and young adults.

Pacific white shrimp (Litopenaeus vannamei) vitelline membrane outer layer protein 1 (VMO1) is produced in the hepatopancreas and transported into ovarian oocytes during vitellogenesis.

In birds, vitelline membrane outer layer protein 1 (VMO1) is an exogenous protein that can be absorbed by eggs as a barrier to prevent the mixing of yolk and egg white. However, researches on VMO1 are limited in birds but not other non-avian species until now. In this study, we first identified a novel Vmo1 cDNA (Lv-Vmo1) in Pacific white shrimp (Litopenaeus vannamei), the most important cultured shrimp in the world. We further analyzed its gene organization, phylogenetic relationship and protein structure. The Lv-Vmo1 transcript was specifically expressed in the hepatopancreas without sexual dimorphism. During ovarian development in female, the hepatopancreatic Lv-Vmo1 mRNA levels showed a significant increase. By in situ hybridization, Lv-Vmo1 mRNA was present in three cell types of the hepatopancreas but neither oocytes nor follicle cells of the ovary. In contrast, immunofluorescence revealed that Lv-VMO1 protein was distributed in the cytoplasms of both hepatopancreatic cells and ovarian oocytes. Western blot showed that Lv-VMO1 protein was produced in the hepatopancreas and transported to the ovary via hemolymph circulation. Identification of a species-specific egg-entry guide protein is the key to the receptor-mediated ovarian transduction of cargo, a novel gene editing approach in oviparous animals. This study lays the mechanism for exogenous transport into penaeid shrimp eggs by VMO1, as a foundation for achieving exogenous protein-mediated incorporation into oocytes.

Preliminary Study on Quantitative Evaluation of Myocardial Fibrosis by CardiacMagnetic Resonance in Patients with Light Chain Cardiac Amyloidosis / 罕见病研究

  Objective  Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (68Ga-FAPI PET).  Methods  We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and 68Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients.  Results  A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high 68Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake.  Conclusions  FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.

A Case Report of Blau Syndrome / 罕见病研究

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients.@*METHODS@#The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro.@*RESULTS@#The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01).@*CONCLUSION@#The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma / 中华内科杂志

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy.

Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as ß-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress.

Early intervention with acupuncture improves the outcome of patients with Bell's palsy: A propensity score-matching analysis.

Objective: Although acupuncture is widely used as a complementary therapy in the treatment of Bell's palsy (BP) when to initiate acupuncture is still controversial. This study aims to determine the efficacy of the early intervention by acupuncture on BP. Methods: We retrospectively gathered clinical data from the Third Affiliated Hospital of SUN-YAT SEN University between 2016 and 2021. We selected newly diagnosed patients with BP who were diagnosed by registered neurologists or acupuncturists formally. The qualified patients were divided into two groups according to whether or not initial acupuncture treatment was given within 7 days from the onset of palsy. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazards modeling and Kaplan-Meier analysis were applied to determine the differences between the two groups. The outcome included time to complete recovery of facial function, the rate of complete recovery, and the occurrence of sequelae in 24 weeks. Results: A total of 345 patients were eligible for this study and were divided into the manual acupuncture/electroacupuncture (MA/EA) group (n = 76) and the EA group (n = 125). In the propensity score-matched cohort, the time to complete recovery was significantly shorter in the MA/EA group compared with the patients in the EA group (hazard ratio 1.505, 95% CI 1.028-2.404, p <0.05). The MA/EA group had a higher rate of favorable outcomes at 12 weeks than the EA group (93.4 vs. 80.3%, p = 0.032), and the occurrence of sequelae at 24 weeks showed a greater reducing trend in the MA/EA group than the EA group (6.6 vs. 16.4%, p = 0.088). Conclusion: Acupuncture intervention at the acute stage of BP could shorten the time to recovery and improve the outcome. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR 2200058060.

Inspiration After Posterior Pharyngeal Flap Palatoplasty: A Preliminary Study Using Computational Fluid Dynamic Analysis.

Posterior pharyngeal flap palatoplasty (PPF) is one of the most commonly used surgical procedures to correct speech, especially for patients suffering from velopharyngeal insufficiency (VPI). During PPF, surgeons use the catheter to control the lateral velopharyngeal port on each side. Airway obstruction and sleep apnea are common after PPF. To understand the air dynamics of the upper airway after PPF, we used computational fluid dynamics (CFD) to demonstrate the airflow. In our previous study, we have revealed the expiration process of the upper airway after PPF and shown the features of how PPF successfully restores the oral pressure for speech. In this study, we focus on examining the inspiration process. Normal airway structures were included. For the normal velopharyngeal structure, one cylinder was applied to each model. For recapitulating the velopharyngeal structure after PPF, two cylinders were used in each model. The ports for borderline/inadequate closure, which can help the oral cavity get the required pressure, were chosen for this study. A real-time CFD simulation was used to capture the airflow through the ports. We found that the airflow dynamics of the upper airway's inspiration were dependent on the velopharyngeal structure. Although the airflow patterns were similar, the velocities between one-port and two-port structures were different, which explained why patients after PPF breathed harder than before and suggested that the one-port structure might be a better choice for secondary VPI reconstruction based on the CFD analyses.

The Role of Structural Deterioration and Biomechanical Changes of the Necrotic Lesion in Collapse Mechanism of Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a crippling disease which is due to a lack of effective therapeutic measures. Its natural progression is rapid, the internal bone structure of the femoral head changes dramatically, and the subsequent fractures and collapse cause severe hip pain and loss of hip function. Femoral head collapse is a critical turning point in the development of ONFH and is related to the prognosis of patients. Early prevention and intervention help to preserve the hip joint and delay femoral head collapse. However, the mechanism of collapse still needs to be further studied because it is affected by different complex factors. This review discusses the underlying causes of femoral head collapse from two aspects: structural degradation and regional changes of biomechanical properties in the necrotic femoral head.

Effect of positive airway pressure on cardiac troponins in patients with sleep-disordered breathing: A meta-analysis.

BACKGROUND: Cardiac troponins are highly sensitive and specific biomarkers for cardiac injury. Previous studies evaluating the effect of positive airway pressure (PAP) on cardiac troponins in patients with sleep-disordered breathing (SDB) have yielded conflicting results. The meta-analysis was performed to examine the effect of PAP on cardiac troponins in SDB patients. METHODS: PubMed, Web of Science, and EMBASE before September 2021 on original English language studies were searched. The data on cardiac troponins in both baseline and post-PAP treatment were extracted from all studies. The data on the change of cardiac troponins in both PAP and control group were extracted from randomized controlled trials. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS: A total of 11 studies were included. PAP treatment was not associated with a significant change in cardiac troponin T between the baseline and post-PAP treatment (SMD = -0.163, 95% confidence interval [CI] = -0.652 to 0.326, z = 0.65, p = .514). The pooled estimate of SMD of cardiac troponin I between the pre- and post-PAP treatment was 0.287, and the 95% CI was -0.586 to 1.160 (z = 0.64, p = .519). The pooled SMD of change of cardiac troponin T between the PAP group and control group was -0.473 (95% CI = -1.198 to 0.252, z = 1.28, p = .201). CONCLUSIONS: This meta-analysis revealed that PAP treatment was not associated with any change of cardiac troponin in SDB patients.

Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications.

BACKGROUND: The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. METHOD: In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. RESULTS: In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. CONCLUSION: This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.

Multidisciplinary Treatment on a Case of ROSAH Syndrome / 罕见病研究

A 15-year-old female was referred to the hospital with intermittent fever, where multiple systemic abnormalities were found, such as splenomegaly, secondary hypersplenism, retinitis pigmentosa, and ectodermal dysplasia. Medical history revealed that she had suffered recurrent respiratory infections, blurred vision at night, and dysplasia of teeth and nail beds since childhood. Then she was suspected to be experiencing ROSAH syndrome, a rare disease newly recognized in recent years, which was finally confirmed by gene sequencing results. During a course of treatment with tumor necrosis factor inhibitors, recurrent fever with elevated inflammatory markers reappeared, and the child developed headaches. To guide the comprehensive treatment and improve the patient's quality of life, the multidisciplinary team in Peking Union Medical College Hospital discussed together and directed the following treatment.

Consensus to 99mTechnetium-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin-related Cardiac Amyloidosis / 罕见病研究

Transthyretin-related amyloid cardiomyopathy (ATTR-CM) is a disease caused by the depo-sition of insoluble amyloid fibers formed by the misfolding of transthyretin precursor protein in the intercellular space of cardiomyocytes. This lesion may lead to myocardial dysfunction, cogestive heart failure, and death.When diagnosed earlier, the patient can be treated with drugs as soon as possible to intervene in the progress of the disease, so as to effectively improve the patient's prognosis.99mtechnetium-pyrophosphate (99Tcm-PYP)single-photon emission computed tomography (SPECT) has been widely used in the imaging examination of cardiac amyloidosis (CA) in recent years. While achieving early non-invasive diagnosis, accurate pathological classification can be obtained through Perugini visual score analysis, semi-quantitative analysis of heart to contralateral lung (H/CL) ratio, and SPECT image analysis. This article presents the application, methods, and the precautions of 99Tcm-PYPSPECT in the diagnosis of ATTR-CM, aiming to provide clinical reference for the application of this technology.

Clinical application of 68Ga-pentixafor PET/CT in surgical diagnosis and prognosis evaluation of primary aldosteronism and correlation analysis of clinical prognosis / 中华泌尿外科杂志

Objective:To explore the clinical value of 68Ga-pentixafor PET/CT targeting for CXCR4 in the diagnosis and prognosis evaluation of primary aldosteronism (PA). Methods:Retrospective analysis was performed on information of 72 patients diagnosed with PA who received operations according to the results of 68Ga-pentixafor PET/CT in our hospital. There were 37 males and 35 females, with the average age of (48.3±9.5) years old. The average lesion diameter was (1.60 ± 0.54)cm. The preoperative systolic and diastolic blood pressure were (177.3 ± 23.9)mmHg and (107.6 ± 13.2)mmHg, respectively. The average preoperative potassium level was (2.62 ± 0.56)mmol/L. The average aldosterone concentration was (17.98 ± 4.66)ng/dl, and the median plasma renin activity was 0.01 (0.01, 0.09) ng/(ml·h). All patients underwent 68Ga-pentixafor PET/CT examination, which lead to the decision of surgical strategies. For those patients with single lesion, multiple lesions in one side or positive lesion in one side but negative in the opposite side, surgical resection of the positive side lesion or total adrenalectomy was considered. For those patients with bilateral positive lesions, surgical resection of the side with more significant positive lesions or total adrenalectomy was considered. For those with negative multiple lesions, the surgical strategy was designed according to the results of CT examination or AVS. The positive rate of 68Ga-pentixafor PET/CT and its relationship with the clinical characteristics and prognosis of patients were analyzed. Results:The results of 68Ga-pentixafor PET/CT were positive in 62 of 72 patients diagnosed with PA (86.1%), and the median SUVmax value was 11.1 (7.1, 16.2). The SUVmax value was positively correlated with the maximum diameter of adrenal lesion ( r=0.468) and negatively correlated with blood potassium levels ( r=-0.437), while not significantly correlated with other clinical characteristics. The positive rate of adenoma by 68Ga-pentixafor PET/CT was higher than that of nodular hyperplasia [90.5%(57/63) vs. 55.6%(5/9), P=0.018], and the SUVmax value in adenoma was also higher than that in nodular hyperplasia [11.9(7.8, 16.2) vs. 4.3(3.4, 11.3), P=0.022]. 32 cases were cured after operations, and 37 cases were improved. And 3 cases were not cured. The SUVmax value of lesions in the cured patients was higher than that in the improved patients [15.4(8.1, 22.7) vs. 10.1(6.8, 13.3), P=0.013]. Among 59 cases of PA patients with single adrenal lesions, 50 cases represented positive results of 68Ga-pentixafor PET/CT. 23 cases in 50 positive cases were cured and 27 cases were improved after resection of positive lesions. In the 13 PA patients with multiple adrenal lesions who underwent surgery according to the results of 68Ga-pentixafor PET/CT, 12 patients (92.3%) showed postoperative prognosis in line with preoperative expectations. Conclusions:68Ga-pentixafor PET/CT showed high positive rate in the diagnosis of PA, especially for adenoma.The SUVmax value of the adrenal lesion was correlated with the blood potassium level, the size of the lesion and the postoperative prognosis. In addition, 68Ga-pentixafor PET/CT could effectively guide the surgical decision of PA.

Clinical value of 18F-FDG PET/CT imaging for detecting immune related adverse events of the combined immunotherapy in hepatobiliary carcinoma / 中华核医学与分子影像杂志

Objective:To investigate the capability of 18F-FDG PET/CT imaging in monitoring combined immunotherapy response and detecting immune related adverse events (irAEs) in patients with advanced hepatobiliary carcinoma. Methods:From August 2018 to July 2019, 21 patients (14 males, 7 females, age (58.5±10.0) years) with advanced hepatobiliary carcinoma routinely underwent 66 18F-FDG PET/CT examinations in Peking Union Medical College Hospital. SUV max, the occurrence time and symptoms of irAEs were obtained and analyzed. Therapy response (complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), progressive metabolic disease (PMD)) was evaluated according to PET response criteria in solid tumors (PERCIST). Results:(1) Clinical results. Twenty-two irAEs occurred in 16 patients, while were not found in 5 patients. Six organs were involved, including thyroiditis(8), colitis(5), pneumonitis(4), rash(2), hepatitis(2), myositis and fasciitis(1). The appearance time of each irAEs were (103.0±58.0), (141.6±103.5), 34.0(6.0, 308.8), 9 and 117, 62 and 67, and 87 d after therapy, respectively. PET/CT detected all pneumonitis and myositis and fasciitis, but no rash and hepatitis were found. For colitis and thyroiditis, PET/CT detected 4 and 6 times respectively. (2) PET/CT signs of irAEs. Except thyroiditis, all irAEs lesions exhibited exudative changes in CT and high-avidity in PET. SUV max of the lesions were 9.0(7.9, 17.6) (colitis), 7.1±3.2 (thyroiditis), 5.3 and 8.6 (pneumonitis), 4.1 (myositis and fasciitis), respectively. (3) Therapy assessment. Among 21 patients, there were 7 for PMR, 9 for SMD, 5 for PMD, which were 7, 8, 1 in patients with irAEs and 0, 1, 4 in patients without irAEs. Conclusions:Patients with advanced hepatobiliary carcinoma can benefit from combined immunotherapy. 18F-FDG PET/CT can be used to evaluate the efficacy of immunotherapy by detecting the changes of tumor lesions and the occurrence of irAEs simultaneously. However, it is necessary to use CT to distinguish tumor progression from irAEs.