Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV.

Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.

ACE2 and COVID-19 and the resulting ARDS.

This article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future. In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising. Trial registration number: NCT04287686.

Renal Cell Carcinoma: the Oncologist Asks, Can PSMA PET/CT Answer?

PURPOSE OF REVIEW: To critically review the potential clinical applications of prostate-specific membrane antigen (PSMA) radioactive ligands in renal cell carcinoma (RCC). RECENT FINDINGS: Radioactive probes targeting PSMA hold promise in several malignancies in addition to prostate cancer, owing to the expression of PSMA by tumor neovasculature. The majority of clear cell RCCs (ccRCC), the most malignant RCC subtype, express PSMA on tumor-associated neovasculature. The endothelium of less aggressive RCC subtypes is PSMA positive in a lower, but still significant percentage of cases. PSMA might therefore represent an interesting theragnostic target in RCC. The preliminary data available suggest a potential role for PSMA-targeting radiopharmaceuticals in complementing conventional imaging for staging ccRCC patients at risk of nodal involvement and oligometastatic disease. Additional applications of PSMA imaging may be the selection and the response assessment of patients receiving anti-angiogenic treatments. The effectiveness of PSMA-targeting radionuclide therapy should also be investigated.

The prognostic value of [123I]-vascular endothelial growth factor ([123I]-VEGF) in glioma.

PURPOSE: Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123I]-VEGF scintigraphy in patients with histologically verified brain tumors. METHODS: 23 consecutive patients (9 women and 14 men aged 30-83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study. All patients had undergone [123I]-VEGF scintigraphy. SPECT examinations of brain were performed 30 min and 18 h after injection. Additional [11C]-methionine PET ([11C]-MET PET) was performed in eight of the 23 patients. Both [123I]-VEGF and [11C]-MET PET were evaluated visually and semiquantitatively by tumor-to-normal brain uptake ratio (T/N ratio). Thresholds of the T/N ratio were evaluated by analysis of receiver operating characteristics (ROC). Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: World Health Organization (WHO) grade IV glioma lesions showed [123I]-VEGF uptake 18 h after the injection, whereas other brain tumors of grade II or III showed negative results. There was no significant difference in the tumor size between VEGF positive and VEGF negative tumors. Patients with [123I]-VEGF T/N ratio threshold <1.32 showed significantly longer survival than patients with T/N ratio ≥ 1.32 (2680 days vs 295 days; P < 0.05). In the subgroup of 16 grade IV glioma patients, significant OS differences were found using a T/N ratio of 1.75 as threshold (T/N ratio < 1.75: 720 days; T/N ≥ 1.75: 183 days; P < 0.05). Significant difference (P < 0.05) was also found in [11C]-MET PET T/N ratios between the grade IV glioma (mean T/N ratio: 3.71) and the grade II or III glioma (mean T/N ratio: 1.74). CONCLUSION: Our results suggest that [123I]-VEGF scintigraphy may be useful for visualization of tumor angiogenesis. In addition, [123I]-VEGF may provide relevant prognostic information in patients with glioma.

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

PURPOSE: This prospective study was to investigate the value of [11C]-acetate PET and [18F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). METHODS: Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [11C]-acetate PET and [18F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. RESULTS: The patient-related sensitivity of [11C]-acetate PET, [18F]-FDG PET, and combined [11C]-acetate and [18F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [11C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. CONCLUSIONS: Our study suggests that combining [18F]-FDG with [11C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo.

PURPOSE: To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early- or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P < .05 indicated a significant difference. RESULTS: Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years ± 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. CONCLUSION: No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.

The role of [18F]F-DOPA PET/CT in diagnostic and prognostic assessment of medullary thyroid cancer: a 15-year experience with 109 patients.

Objective: Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC. Methods: We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan-Meier, and Cox regression analyses were performed. Results: In total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS. Conclusion: [18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.

Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid Aß and τ level.

BACKGROUND: Accumulation of ß-amyloid protein (Aß) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aß levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aß and tau in humans. METHODS: The participants were assigned into spinal anesthesia (N=35), spinal plus desflurane anesthesia (N=33), or spinal plus isoflurane anesthesia (N=38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aß (Aß40 and Aß42) and total tau in the CSF were determined. RESULTS: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aß40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P=0.022. Desflurane, but not isoflurane, was associated with a decrease in Aß42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P=0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. CONCLUSIONS: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aß levels.

His-Purkinje conduction system pacing and atrioventricular node ablation in treatment of persistent atrial fibrillation refractory to multiple ablation procedures: A case report.

In patients with symptomatic atrial fibrillation refractory to optimal medical therapy, atrioventricular node ablation followed by permanent pacemaker implantation is an effective treatment option. A 66-year-old woman with symptomatic persistent atrial fibrillation refractory to multiple ablation procedures was referred to our institution. After optimal drug therapy, the patient still had obvious symptoms. Sequential His-Purkinje conduction system pacing and atrioventricular node ablation were performed. Left bundle branch pacing was used as a backup pacing method if thresholds of His bundle pacing were too high or loss of His bundle capture occurred in the follow-up. At the 6-month follow-up, the European Heart Rhythm Association classification for AF was improved, the score of the Atrial Fibrillation Effect on Quality of Life was enhanced, and the 6-Minute Walk Test was ameliorated. The present case was subjected to His-Purkinje conduction system pacing in combination with atrioventricular node ablation as treatment for a symptomatic persistent atrial fibrillation refractory to multiple ablation procedures, and this procedure alleviated symptoms and improved the quality of life in a short-term follow-up.

Corrigendum: Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

[This corrects the article DOI: 10.3389/fneur.2022.956931.].

His-Purkinje conduction system pacing combined with atrioventricular node ablation improves quality of life in older patients with persistent atrial fibrillation refractory to multiple ablation procedures.

BACKGROUND: Recurrence of atrial fibrillation (AF) is common in patients with persistent AF even after multiple ablation procedures. His-Purkinje conduction system pacing (HPCSP) combined with atrioventricular node ablation (AVNA) is effective in managing patients with AF and heart failure. This study aimed to determine whether HPCSP combined with AVNA can improve quality of life and alleviate symptoms in older patients with symptomatic persistent AF refractory to multiple ablation procedures, as well as evaluate the feasibility and safety of this therapy. METHODS: Older patients (≥ 65 years) with symptomatic persistent AF refractory to at least two ablation procedures were treated with combined HPCSP and AVNA. The success rates and complications were recorded. Pacing parameters, European Heart Rhythm Association (EHRA) scores, and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) scores obtained perioperatively were compared with those recorded at the 6-month follow-up examination. RESULTS: Thirty-one patients were enrolled; of those, only thirty patients were eventually treated with AVNA because one patient developed a complete atrioventricular block following the withdrawal of the His bundle pacing lead. The success rates were 100% for HPCSP (22 cases with His bundle pacing, and 9 cases with left bundle branch pacing) and 93.3% (28/30) for AVNA, respectively. By the 6-month follow-up examination, EHRA scores improved significantly (3.00 ± 0.73 vs. 2.44 ± 0.63, P = 0.014) and AFEQT scores increased markedly (49.6 ± 20.6 vs. 70.9 ± 14.0, P = 0.001). No severe complications developed. CONCLUSIONS: When used in older patients with symptomatic persistent AF refractory to multiple ablation procedures, HPCSP combined with AVNA significantly alleviated symptoms and improved quality of life during short-term follow-up. This therapy was proved to be safe and effective in this patient population.

Efficacy of scalp stimulation for multidomain cognitive impairment in patients with post-stroke cognitive impairment and dementia: A network meta-analysis and meta-regression of moderators.

BACKGROUND: Scalp stimulation has gained more traction for post-stroke cognitive impairment and dementia (PSCID); the interaction between stimulation targets and parameters influences the response to the stimulation. However, the most efficacious treatment for improving different domains of cognitive impairment remains unknown. OBJECTIVE: We aimed to conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of various scalp stimulation protocols used in PSCID treatment. METHODS: Randomized controlled trials of scalp stimulation in patients with PSCID were searched in eight databases over the past 20 years. Standardized mean differences (SMDs) for global and subdomain cognitive scores were pooled in Bayesian NMA. Moderators were examined using meta-regression analysis. RESULTS: A total of 90 trials, with 6199 patients, were included. Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected dorsolateral prefrontal cortex (DLPFC) was highly suggested for alleviating global severity (SMD = 1.11, 95% CI (0.64, 1.57)). High-frequency rTMS over the left DLPFC was recommended for language use (1.85 (1.18, 2.52)), executive function (0.85 (0.36, 1.33)), orientation deficits (0.59 (0.07, 1.13)), and attention (0.85 (0.27, 1.43)). Anodal transcranial direct current stimulation over the affected DLPFC (2.03 (0.72, 3.34)) was recommended for treating memory impairment. Meta-regression analyses showed significant associations within attention, language and orientation. CONCLUSION: Overall, different cognitive domains have different optimal scalp stimulation prescriptions, and activating the affected key brain regions and inhibiting the unaffected area is still the most effective treatment.

Efficacy and safety of single-pill amlodipine/losartan versus losartan in patients with inadequately controlled hypertension after losartan treatment: a multicenter, double-blind, randomized phase III clinical trial.

Objective: Single-pill amlodipine besylate (AML) plus losartan (LOS) has been used to treat inadequately controlled hypertension after antihypertensive monotherapy; however, relevant data in China are limited. This study aimed to compare the efficacy and safety of single-pill AML/LOS and LOS alone in Chinese patients with inadequately controlled hypertension after LOS treatment. Methods: In this multicenter, double-blind, randomized, controlled phase III clinical trial, patients with inadequately controlled hypertension after 4 weeks of LOS treatment were randomized to receive daily single-pill AML/LOS (5/100 mg, AML/LOS group, N = 154) or LOS (100 mg, LOS group, N = 153) tablets for 8 weeks. At weeks 4 and 8 of treatment, sitting diastolic and systolic blood pressure (sitDBP and sitSBP, respectively) and the BP target achievement rate were assessed. Results: At week 8, the sitDBP change from baseline was greater in the AML/LOS group than in the LOS group (-8.84 ± 6.86 vs. -2.65 ± 7.62 mmHg, P < 0.001). In addition, the AML/LOS group also showed greater sitDBP change from baseline to week 4 (-8.77 ± 6.60 vs. -2.99 ± 7.05 mmHg) and sitSBP change from baseline to week 4 (-12.54 ± 11.65 vs. -2.36 ± 10.33 mmHg) and 8 (-13.93 ± 10.90 vs. -2.38 ± 12.71 mmHg) (all P < 0.001). Moreover, the BP target achievement rates at weeks 4 (57.1% vs. 25.3%, P < 0.001) and 8 (58.4% vs. 28.1%, P < 0.001) were higher in the AML/LOS group than those in the LOS group. Both treatments were safe and tolerable. Conclusion: Single-pill AML/LOS is superior to LOS monotherapy for controlling BP and is safe and well tolerated in Chinese patients with inadequately controlled hypertension after LOS treatment.

The effects of isoflurane and desflurane on cognitive function in humans.

BACKGROUND: The etiology of postoperative cognitive decline (POCD) remains to be determined. Anesthetic isoflurane, but not desflurane, may induce neurotoxicity. However, the functional consequences of these effects have not been assessed. We therefore performed a pilot study to determine the effects of isoflurane and desflurane on cognitive function in humans. METHODS: The subjects included patients who had lower extremity or abdominal surgery under spinal anesthesia alone (S, n = 15), spinal plus desflurane anesthesia (SD, n = 15), or spinal plus isoflurane anesthesia (SI, n = 15) by randomization. Each of the subjects received cognitive tests immediately before and 1 week after anesthesia and surgery administered by an investigator who was blinded to the anesthesia regimen. POCD was defined using the scores from each of these tests. RESULTS: We studied 45 subjects, 24 males and 21 females. The mean age of the subjects was 69.0 ± 1.9 years. There was no significant difference in age and other characteristics among the treatment arms. The mean number of cognitive function declines in the S, SD, and SI groups was 1.13, 1.07, and 1.40, respectively. POCD incidence after SI (27%), but not SD (0%), anesthesia was higher than that after S (0%), P = 0.028 (3-way comparison). CONCLUSION: These findings from our pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed.

[Effects of naoxintong capsule on the inflammation and prognosis in borderline lesion coronary heart disease patients].

OBJECTIVE: To study the effects of Naoxintong Capsule (NC) on the inflammation and long-term prognosis in the borderline lesion coronary heart disease patients. METHODS: A total of 240 coronary heart disease patients with angina symptoms and accompanied with borderline lesion coronary heart disease (with the diameter stenosis in critical 50% -70%) by means of coronary angiography or multislice computed tomography coronary angiography were recruited. These patients were randomly assigned to the conventional treatment group (including nitrate, beta blockers, anti-platelet, anticoagulation, angiotensin converting enzyme inhibitors, and so on) and the NC treatment group (treated the same way as those for the conventional treatment group and NC). All patients were treated for 12 months. The occurrence of cardiovascular events was observed after treatment. The inflammatory factors in serum [interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and high sensitive C reaction protein (hs-CRP)], matrix metalloproteinases-9 (MMP-9), blood lipids and blood sugar, liver and kidney functions were measured before and after treatment. RESULTS: After 12 months of treatment, the incidence of angina pectoris patients (6.67% vs 15.83%, P < 0.05) and hospitalization due to acute coronary syndrome (ACS) attacks (4.17% vs 10.83%) was significantly lower in the NC treatment group than in the conventional treatment group. There was no statistical difference in the serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 between the two groups before treatment (P > 0.05). After 12 months of treatment, serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 were significantly lower when compared with before treatment in the same group (P < 0.05). Besides, the serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 were significantly lower in the NC group than in the conventional treatment group (P < 0.05). By means of Logistic regression analysis we found that the post-treatment MMP-9 level and IL-6 level were independent risk factors influencing the recurrence of angina pectoris. CONCLUSIONS: NC could alleviate the inflammation. Long-term administration of NC could reduce the recurrence of angina pectoris and decrease the incidence of ACS attack in borderline lesion coronary heart disease patients. The post-treatment MMP-9 level and IL-6 level were independent risk factors influencing the recurrence of angina pectoris.

Diagnostic Value of 2-[18F]FDG PET/CT in a Patient with Atypical Subacute Thyroiditis: A Case Report.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) imaging with 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) is a sensitive diagnostic imaging modality in oncology and could be a useful diagnostic tool in patients with fever of unknown origin (FUO) or with inflammation of unknown origin (IUO). CASE PRESENTATION: We report a case of a patient originally presenting with a clinical history of FUO and later with persistent high-sensitivity C-reactive protein (hsCRP) levels, even after antibiotic therapy. The patient underwent 2-[18F]FDG PET/CT to investigate and to localize a possible focus of infection or inflammation. 2-[18F]FDG hotspots were detected in both thyroid lobes. Thyroid diagnostic examinations and follow up were performed. Subacute thyroiditis (SAT) was then diagnosed by thyroid examinations, and other possible causes of FUO or IUO were not found. CONCLUSION: This case illustrates the potential diagnostic value of 2-[18F]FDG PET/CT in patients with atypical SAT, who originally present with only a clinical history of FUO.

Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC).

PURPOSE: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC. METHODS: Five patients (all female, mean age 62 ± 8 years, ranged from 51 to 69 years) with distant metastatic DTC (dmDTC) after total thyroidectomy (TTE) and neck lymph node dissection were treated with apatinib at a dose 500 mg per day after 18F-Fluorodeoxyglucose (18F-FDG) PET/CT. The effects of apatinib on DTC were evaluated at 4 ± 1 months after treatment with apatinib. RAI therapy was then initiated. The response to apatinib and the combination therapy with RAI treatment was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1) and metabolic activity using serum thyroglobulin (Tg) and 18F-FDG PET/CT. RESULTS: Positive 18F-FDG PET/CT results were found in all patients before apatinib therapy. The immunohistochemical analysis of primary tumour tissues showed high expression of vascular endothelial growth factor receptor-2 (VEGFR-2). Four patients with follicular thyroid carcinoma (FTC) showed partial response (PR) with significant decrease in tumour size and maximum standardized uptake value (SUVmax) after 4 ± 1 month's treatment with apatinib. Further significant reduction of tumour size and SUVmax were observed in three patients after combination therapy with apatinib and RAI. Only one patient with both FTC and papillary thyroid cancer (PTC) demonstrated progressive disease (PD) after treatment with apatinib alone, however, a decrease in tumour size and SUVmax as well as serum Tg levels was achieved after the combination with RAI therapy and apatinib. CONCLUSIONS: Apatinib had significant antitumour effects on progressive distant metastatic DTC. Moreover, beneficial synergistic and complementary effects were shown when apatinib combined with RAI therapy. CLINICAL TRIAL REGISTRATION: NCT04180007, Registered November 26, 2019.

Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

Introduction: Post-stroke aphasia (PSA) is a language disorder caused by left hemisphere stroke. Electroacupuncture (EA) is a minimally invasive therapeutic option for PSA treatment. Tongli (HT5) and Xuanzhong (GB39), two important language-associated acupoints, are frequently used in the rehabilitation of patients with PSA. Preliminary evidence indicated functional activation in distributed cortical areas upon HT5 and GB39 stimulation. However, research on the modulation of dynamic and static functional connectivity (FC) in the brain by EA in PSA is lacking. Method: This study aimed to investigate the PSA-related effects of EA stimulation at HT5 and GB39 on neural processing. Thirty-five participants were recruited, including 19 patients with PSA and 16 healthy controls (HCs). The BOLD signal was analyzed by static independent component analysis, generalized psychophysiological interactions, and dynamic independent component analysis, considering variables such as age, sex, and years of education. Results: The results revealed that PSA showed activated clusters in the left putamen, left postcentral gyrus (PostCG), and left angular gyrus in the salience network (SN) compared to the HC group. The interaction effect on temporal properties of networks showed higher variability of SN (F = 2.23, positive false discovery rate [pFDR] = 0.017). The interaction effect on static FC showed increased functional coupling between the right calcarine and right lingual gyrus (F = 3.16, pFDR = 0.043). For the dynamic FC, at the region level, the interaction effect showed lower variability and higher frequencies of circuit 3, with the strongest connections between the supramarginal gyrus and posterior cingulum (F = 5.42, pFDR = 0.03), middle cingulum and PostCG (F = 5.27, pFDR = 0.036), and triangle inferior frontal and lingual gyrus (F = 5.57, pFDR = 0.026). At the network level, the interaction effect showed higher variability in occipital network-language network (LN) and cerebellar network (CN) coupling, with stronger connections between the LN and CN (F = 4.29, pFDR = 0.042). Dynamic FC values between the triangle inferior frontal and lingual gyri were anticorrelated with transcribing, describing, and dictating scores in the Chinese Rehabilitation Research Center for Chinese Standard Aphasia Examination. Discussion: These findings suggest that EA stimulation may improve language function, as it significantly modulated the nodes of regions/networks involved in the LN, SN, CN, occipital cortex, somatosensory regions, and cerebral limbic system.

Genome sequence of Rhodococcus sp. strain R04, a polychlorinated-biphenyl biodegrader.

The genus Rhodococcus has proved to be a promising option for the cleanup of polluted sites and application of a microbial biocatalyst. Rhodococcus sp. strain R04, isolated from oil-contaminated soil, can biodegrade polychlorinated biphenyls. Here we report the draft genome sequence of Rhodococcus sp. strain R04, which could be used to predict genes for xenobiotic biodegradation and provide important insights into the applications of this strain.