Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Involvement of glyphosate in disruption of biotransformation P450 enzymes and hepatic lipid metabolism in chicken.

The current study investigated the potentially harmful consequences of pure glyphosate or Roundup® on CYP family members and lipid metabolism in newly hatched chicks. On the sixth day, 225 fertilized eggs were randomly divided into three treatments: (1) the control group injected with deionized water, (2) the glyphosate group injected with 10 mg pure glyphosate/Kg egg mass and (3) the Roundup group injected 10 mg the active ingredient glyphosate in Roundup®/Kg egg. The results of the study revealed a reduction in hatchability in chicks treated with Roundup®. Moreover, change of Lipid concentration in serum and the liver-treated groups. Additionally, increased liver function enzymes and increased oxidative stress in the glyphosate and Roundup® groups. Furthermore, liver tissues showed histological changes and several lipid deposits in glyphosate-treated groups. Hepatic CYP1A2 and CYP1A4 expressions were significantly increased (p < .05) after glyphosate exposure, and suppression of CYP1C1 mRNA expression was significant (p < .05) after Roundup® exposure. The pro-inflammatory cytokines genes IFN-γ and IL-1ß expression were significantly increased (p < .05) after Roundup® exposure. In addition, there were significant differences in the levels of expression genes which are related to lipid synthesis or catabolism in the liver. In conclusion, in ovo glyphosate exposure caused disruption of biotransformation, pro-inflammatory and lipid metabolism in chicks.

The preliminary experience of immediate radical prostatectomy after the diagnosis of prostate cancer by targeted prostate biopsy combined with intraoperative frozen section / 中华老年医学杂志

Objective:To investigate the practicality and safety of performing a radical prostatectomy(RP)shortly after the diagnosis of prostate cancer using a combination of prostate targeted biopsy and intraoperative frozen section.Methods:Prospective enrollment was conducted for patients suspected of having prostate cancer based on abnormal prostate specific antigen(PSA)levels.The inclusion criteria for the study were as follows: patients aged 80 years or younger with an ECOG score of 1 or lower.Prior to biopsy, patients underwent both prostate magnetic resonance imaging(MRI)and prostate specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)to determine the likelihood of prostate cancer with clinical stages within T 2-3aN 0M 0.In order to be included in the study, patients must agree to receive RP after their prostate cancer diagnosis has been confirmed by biopsy.All enrolled patients underwent a targeted prostate biopsy, consisting of 1-2 cores.These specimens were then examined through frozen section analysis.For patients diagnosed with prostate cancer through intraoperative frozen section pathology, RP was immediately performed.In this study, transperineal prostate targeted+ systematic biopsy was utilized for patients with undiagnosed prostate cancer.Additionally, routine pathological examination of specimens was conducted.The study analyzed the baseline data, surgical conditions, pathological results, and follow-up information of patients in a descriptive manner. Results:Seven patients, ranging in age from 54 to 77 years with a mean age of 66.7 years, were enrolled in the study.Their mean PSA level was 12.668 μg/L, ranging from 4.359 to 22.195 μg/L.Of these patients, 4 had a PI-RADS score of 4 and 3 had a score of 5.The maximum diameter of the index lesion was 1.3 cm, ranging from 0.5 to 2.2 cm.PSMA PET/CT scores were 4 in 1 case and 5 in 6 cases.The index lesions detected by PSMA PET/CT were consistent with those detected by MRI, and the maximum standardized uptake value(SUVmax)was 15.7, ranging from 5.3 to 39.4.Prostate cancer was diagnosed through targeted biopsy and intraoperative frozen section pathology.Four cases had a Gleason score of 3+ 3=6, while one case had a Gleason score of 3+ 4=7, another had a score of 4+ 3=7, and the last had a score of 4+ 4=8.All patients underwent RP treatment immediately after the prostate cancer diagnosis.Only one patient had slight adhesion at the apex of the prostate, while the other six patients were evaluated by surgeons as having no obvious adhesion at the apex.All surgeries were completed successfully, with a mean operation time of 149.7(ranging from 108 to 255)minutes.After RP, whole mount pathology results indicated that all cases were prostate adenocarcinoma, with a Gleason score of 3+ 4=7 in four cases and 4+ 3=7 in three cases.The pathological stages were pT2 in three cases and pT3a in four cases, with five cases having negative surgical margins and two cases with positive surgical margins.During the study, all patients were monitored for a period of 5.4 months(ranging from 3 to 7 months)and no complications of Clavien Dino≥Ⅰ were observed.PSA levels were measured at 6 weeks and 3 months after surgery, with readings of 0.020 μg/L(ranging from 0 to 0.079 μg/L)and 0.016 μg/L(ranging from 0 to 0.087 μg/L), respectively.No hormonal therapy or radiotherapy was administered during this time.Four patients were able to recover from urinary continence.Conclusions:Based on a combination of MRI and PSMA PET/CT, it is both safe and feasible to promptly perform RP following the diagnosis of prostate cancer through targeted biopsy for index lesions, along with intraoperative frozen section.

Correlation between serum zinc and brain injury in infants with mild gastroenteritis complicated with benign infantile convulsion and febrile convulsion / 中华危重病急救医学

Objective:To investigate the association between serum zinc levels and convulsive brain injury in infants with mild gastroenteritis complicated with benign infantile seizures (BICE) and febrile seizures (FC).Methods:A case-control study method was conducted. 120 children with mild gastroenteritis and convulsion admitted to the First Affiliated Hospital of Hebei North University from January 2020 to January 2022 were enrolled as the research subjects. They were divided into BICE group and FC group according to the type of convulsion. The serum zinc level, the frequency and duration of convulsion, and the occurrence of convulsive brain injury in the two groups were recorded. Multivariate Logistic regression analysis was used to screen the risk factors for convulsive brain injury. The Spearman correlation method was used to analyze the association between serum zinc levels, clinical characteristics of convulsion and convulsive brain injury.Results:A total of 120 children were enrolled, of which 81 developed to BICE and 39 developed to FC during hospitalization. The serum zinc level of children in the FC group was significantly lower than that in the BICE group (μmol/L: 39.24±6.50 vs. 48.65±7.21, P < 0.01). In the BICE group and FC group, the serum zinc level in children with more than 2 convulsions was significantly lower than that in the children with one convulsion (μmol/L: 37.65±6.50 vs. 53.17±7.55 in the BICE group, and 30.27±5.58 vs. 44.16±7.57 in the FC group, both P < 0.01). Serum zinc level in children with convulsion duration ≥5 minutes was significantly lower than that in the children with convulsion duration < 5 minutes (μmol/L: 38.75±6.74 vs. 51.21±7.58 in the BICE group, and 31.08±5.46 vs. 45.19±7.25 in the FC group, both P < 0.01). Moreover, the serum zinc level of children with different convulsion frequency and duration in the FC group was significantly lower than that in the BICE group (all P < 0.01). Among the 120 children, 9 cases of convulsive brain injury occurred, and the incidence rate was 7.50%. The incidence of convulsive brain injury in the BICE group was 1.23% (1/81), which was significantly lower than 20.51% in the FC group (8/39, P < 0.01). The serum zinc level of children with convulsive brain injury was significantly lower than that of children with non-brain injury (μmol/L: 28.50±5.00 vs. 60.22±7.31, P < 0.01), and the number of convulsion was significantly higher than that of non-cerebral injury (≥ 2 convulsions: 100.00% vs. 1.80%, P < 0.01), and the duration of convulsion in children with brain injury was significantly longer than that of non-brain-injured children (convulsion duration ≥5 minutes: 100.00% vs. 11.71%, P < 0.01). Multivariate Logistic regression analysis showed that decreased serum zinc level [odds ratio ( OR) = 2.147, 95% confidence interval (95% CI) was 1.354-3.403], increased number of convulsion ( OR = 3.452, 95% CI was 1.266-9.417), and prolonged convulsion duration ( OR = 3.117, 95% CI was 1.326-7.327) were independent risk factor for convulsive brain injury in children with mild gastroenteritis and convulsion (all P < 0.05). Spearman correlation analysis showed that serum zinc level, convulsion ≥2 times, duration of convulsion ≥5 minutes and convulsion ≥2 times + convulsion duration ≥5 minutes were significantly negatively correlated with the occurrence of convulsive brain injury in FC children ( r values were -0.546, -0.517, -0.522, and -0.528, all P < 0.01). There was no significant correlation between serum zinc level, convulsion ≥2 times, convulsion duration ≥5 minutes and convulsion ≥2 times+convulsion duration ≥5 minutes and convulsive brain injury in BICE children ( r values were -0.281, -0.129, -0.201, -0.243, all P > 0.05). Conclusions:Serum zinc level is related to the characteristics of convulsive symptoms in children with mild gastroenteritis complicated with FC, and has a strong negative correlation with the occurrence of convulsive brain injury. Active targeted intervention and treatment may help reduce the incidence of brain injury in children.

Analysis on Ethical Review of Real-world Research in Pediatric Population / 中国医学伦理学

【Objective:】 To analyze and explore the key points of the ethical review of real-world research in pediatric population, and to provide reference for ethical review of real-world research in pediatric population. 【Methods:】 According to the characteristics of real-world research and pediatric clinical trials, the review points of real-world research in pediatric population were analyzed and discussed in comparison with the principles and focus of ethical review in general clinical research. 【Results:】 The ethics committee should pay particular attention to the review of informed consent, privacy protection, risk benefit assessment, cost and compensation, and should also take into account the research design, data governance, research conflicts of interest, research registration and publication, etc., and conduct scientific and reasonable ethical review of real-world research in pediatric population. 【Conclusion:】 Clinical trials in pediatric population should have stricter and scientific ethical review, which can not only protect the interests of vulnerable groups of minors, but also standardize real-world research in pediatric population and promote the healthy development of pediatric clinical research, so as to better protect children and promote their health.

Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions: a retrospective study

BackgroundPeople living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among infected patients and should be prioritized in vaccination program. In this retrospective study, we assessed the safety and immunogenicity of the CoronaVac inactivated vaccines in people with underlying medical conditions to address the vaccine hesitation in this special population. MethodsIn this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary heart disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was geometric mean titer (GMT) of neutralizing antibodies to living SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after full two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281) and is active but no longer recruiting. FindingsAmong 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse reactions was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy group, with significant difference (P=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some groups. Most adverse reactions were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and GMT of neutralizing antibody showed no significant difference between disease group and healthy group, except CAD group (P=0.03) and CRD group (P=0.04) showed slight reduction. By day 90, the neutralizing antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralizing antibody continued to decrease in each group, but with slower declination. InterpretationFor people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the evidence to address vaccine hesitancy for seniors and people living with chronic diseases. FundingYunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), Sinovac Biotech Ltd (PRO-nCOV-4004).

Evaluation of left ventricular function by treadmill exercise stress echocardiography combined with layer-specific strain technique in essential hypertension patients.

The purpose of this study was to evaluate the diagnostic utility of treadmill exercise stress echocardiography (TESE) combined with left ventricular (LV) layer-specific strain (LSS) in subclinical myocardial and reserve function of hypertensive patients. A total of 55 hypertensive patients and 51 controls were evaluated during rest and exercise. Two-dimensional speckle tracking (2DST) and LSS technique was used to measure longitudinal and circumferential strains at rest and peak exercise, strain difference characteristics were then evaluated. Compared to the control subjects, both longitudinal and circumferential LSS showed different degrees of reduction in hypertensive group, which was more pronounced at peak exercise. The global longitudinal endocardium strain (GLSendo) at rest was 24.4% ± 1.5% in the control group versus 20.4% ± 2.3% in the hypertensive group, while the difference was more obvious at peak state (control vs. hypertensive group, 30.8% ± 2.8% and 22.8% ± 2.9%, respectively). In particular, endocardial strain under exercise can be used as a sensitive indicator where the LV contractile reserve (CR) function of the three layers are all impaired. TESE combined with LSS might increase diagnostic accuracy of myocardial performance in hypertension patients.

Diagnostic value of 18F-prostate specific membrane antigen PET/CT combined with multiparametric-MRI in identifying the grade group of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the diagnostic value of the combination of 18F-prostate specific membrane antigen (PSMA) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in identifying the grade group of prostate cancer, using parameters derived from the two imaging modalities. Method:Prostate cancer patients diagnosed by histopathology and received 18F-PSMA PET/CT and mpMRI during September 2018 to May 2021 in our hospital were retrospectively studied. The median age was 68(64-75), with the median PSA level of 14.74(7.75-24.19)ng/mL. All patients received mpMRI before biopsy. On biopsy, 6(12.2%) patients had International Society of Urological Pathology grade group(ISUP GG) 1 diseases, 16(32.7%) had ISUP GG 2 diseases, 12(24.5%) had ISUP GG 3 diseases, and 15(10.9%) had ISUP GG 4 or 5 diseases. Patients were then divided into high-grade group (ISUP 4-5) and low-grade group(ISUP 1-3). The median age of patients in high-grade group and low-grade group were 65(62-76) and 71(65-74), respectively. The PSA level in high-grade group and low-grade group were 15.11(6.63-42.86) ng/ml and 12.31(7.94-18.25) ng/ml, respectively. No significant differences were found in age and PSA level between the two groups ( P=0.334, P=0.448). All patients underwent 18F-PSMA PET/CT within 4 weeks after biopsy. The maximum standardized uptake value(SUV max) and the minimum apparent diffusion coefficient(ADC min)were recorded, and the ratio of SUV max/ ADC minwere calculated. The correlation between the above parameters and ISUP grade group were analyzed.The diagnostic value of the parameters was evaluated by the receiver operating characteristic (ROC) curve. Results:The data of 49 patients were analyzed. The average ADC minwas (0.57±0.16)×10 -3 mm 2/s, with the average SUV max and SUV max/ADC min of 15.30±12.54 and (29.69±23.72)×10 3, respectively. Statistical differences were found in SUV max ( P=0.012) and SUV max/ADC min ( P=0.002) between the high- and low-grade groups, while ADC min ( P=0.411) showed no statistical differences between the two groups. Significant positive correlations were found between SUV max(r=0.501, P<0.001), SUV max/ADC min (r=0.527, P<0.001) and ISUP grade group, respectively. There was a negative correlation between ADC min and ISUP grade group (r=-0.296, P=0.039). SUV max/ADC min was the best index to distinguish high-grade group from low-grade group prostate cancer with the area under the curve(AUC) of 0.749. In contrast, the AUC of SUV maxand ADC min were 0.731 and 0.615, respectively. The diagnostic sensitivity and specificity of SUV max/ADC min were 73.3% and 85.3%, respectively, with a critical value of 37.23×10 3. Conclusion:The combination use of 18F-PSMA PET/CT and mpMRI could improve the diagnostic efficiency for prostate cancer, compared to either modality alone. The ratio of SUV max/ADC min has a positive correlation with ISUP grade group, and is a promising index for distinguishing the high-grade prostate cancer from low-grade cancer.

Grey matter alterations in patients with Parkinson′s disease with different sleep disorders / 中华神经科杂志

Objective:To investigate the grey matter alterations of Parkinson′s disease (PD) patients with and without sleep disorders, and to explore the relationship between different sleep-related problems and clinical variables as well as grey matter volume (GMV) in PD.Methods:Forty-six PD patients and 38 healthy controls (HCs) were recruited from January 2018 to December 2021 in the Department of Neurology, Beijing Hospital. PD patients were divided into PD with sleep disorders (PD-S, n=26) and PD without sleep disorders (PD-nS, n=20) subgroups (cutoff points of 82 for Parkinson′s Disease Sleep Scale or less than 5 for each item was considered as an indicator of substantial sleep disorder). The Mini-Mental State Examination (MMSE), the third part of the Unified Parkinson′s Disease Rating Scale (UPDRS-Ⅲ), Hamilton Rating Scale for Anxiety (HAMA), Hamilton Rating Scale for Depression (HAMD), Non-Motor Symptoms Questionnaire (NMSQ), and Parkinson′s Disease Questionnaire-39 (PDQ-39) were used to evaluate cognitive function, motor symptoms, anxious and depressive symptoms, non-motor symptoms, and the quality of life of the patients. Optimized voxel-based morphometry was applied to the magnetic resonance imaging brain images in all participants,and multiple linear regression analysis was used to test the correlation between GMV and sleep quality in patients with PD. Results:Compared with the HCs, PD-nS patients showed decreased GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, cingulate gyrus, hippocampus, right cerebellum, bilateral frontotemporal lobe, bilateral occipital lobe and the left parietal lobe. PD-S group exhibited reduced GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, right cerebellum, bilateral frontotemporal lobe and bilateral parietal-occipital lobe, compared to the HCs. Compared with PD-nS, PD-S patients revealed higher depressive (HAMD score: 12.19±5.59 vs 6.95±3.19, t=-4.01, P<0.001), anxious (HAMA score: 12.04±5.32 vs 7.25±4.68, t=-3.18, P=0.003), and non-motor symptoms scores (NMSQ score: 12.92±5.18 vs 9.90±4.10, t=-2.14, P=0.038), poorer quality of life (PDQ-39 score: 35.31±22.01 vs 22.40±9.00, t=-2.71, P=0.010), and reduced GMV in the left insula, frontal, and parietal lobe ( P<0.001, uncorrected, cluster>100). There was a marked relationship between sleep quality and the reduced GMV of the right medial temporal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.003), left middle frontal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.002), the right cerebellum (β=0.014, 95% CI 0.005-0.023, P=0.003), and the right medial occipital gyrus (β=0.017, 95% CI 0.011-0.024, P<0.001). Significant grey matter changes were associated with nocturnal restlessness, mainly within the left limbic lobe, bilateral occipital lobe, the right cerebellum, and parietal lobe (β=0.008, 95% CI 0.006-0.010, P<0.001). Furthermore, nocturia in PD was related to certain grey matter atrophy, including bilateral limbic lobe, the right inferior parietal gyrus, and bilateral frontal lobe (β=0.010, 95% CI 0.008-0.013, P<0.001). The symptom of daytime dozing was correlated with GMV reduction in the right occipital lobe, the left temporal lobe (β=0.014, 95% CI 0.010-0.019, P<0.001). There were also several compensatory brain regions, including bilateral frontal lobe, the left limbic lobe and cingulate ( P<0.001, uncorrected, cluster>60). Conclusions:Sleep disturbance is common in PD, which is related to the anxious and depressive symptoms, non-motor symptoms, and the quality of life. PD patients with different sleep disorders show grey matter alterations in severeal brain regions, which are associated with sleep quality, nocturnal restlessness, psychosis, and daytime dozing.

The preliminary study about feasibility and accuracy of the frozen section during targeted prostate biopsy / 中华泌尿外科杂志

Objective:To investigate the feasibility and reliability of the frozen section during targeted prostate biopsy.Methods:The clinical and pathological information of patients who received cognitive fusion transperineal targeted plus systematic biopsy and frozen section of 1-2 core targeted biopsy were consecutively collected and retrospectively studied. The median age was 70 (ranging 64-78) years, with the median prostate-specific antigen (PSA) level of 11.00 (ranging 6.63-16.52) ng/ml and the median prostate volume of 35.72 (ranging 22.59-47.71) ml. All patients received bi-parametric magnetic resonance imaging (bp-MRI) and have Prostate Imaging Reporting and Data System (PI-RADS) 3 or higher lesions diagnosed on bp-MRI. The suspected lesions would be taken by targeted biopsy of which one or two cores would be sent to prepare for the frozen sections. Then a cognitive fusion targeted and systematic biopsy covering the above targeted zones would be routinely administered under a transperineal approach as a standard protocol. The total time used for diagnosis of the frozen sections, the pathological diagnosis and the International Society of Urological Pathology (ISUP) grade groups (GG) would be recorded. The sensitivity, the positive predictive value, and the accuracy on grade groups would be analyzed, using the pathological diagnosis based on standard sections from the same targeted lesion.Results:A total of 29 patients were included in this study. Accordingly, 29 suspected lesions were identified on bp-MRI. A total of 20 lesions were finally diagnosed of PCa on frozen section, with the detection rate of 69.0%. Of those, 9(45.0%) cases were ISUP GG 1 diseases, 5(25.0%) cases were GG 2 diseases, 1(5.0%) case was GG 3 disease, and 5(25.0%) cases were GG 4-5 diseases. A total of 22 lesions were diagnosed with PCa on standard sections of cores from the same targeted lesions, with the detection rate of 75.9%. Of those, 6(27.3%) cases were GG 1 disease, 11(50.0%) cases were GG 2 diseases, 1(4.5) case was GG 3 disease, and 4(18.2%) cases were GG 4-5 diseases. The sensitivity and the positive predictive value of frozen section were 90.9% and 100%, respectively. No false positive diagnosis was made by frozen section. Compared to diagnosis from frozen sections, the GG diagnosed from final standard sections were found to upgrade and downgrade in 2 and 2 cases, respectively. The accuracy rate on GG of frozen sections was 80%. The time used for the diagnosis of frozen sections was (11±2) minutes. The histology quality control of four specimens was dissatisfactory. Two were due to tissue loss and deformation during sampling, and the other two were due to cytoclasis during low-temperature transferring.Conclusion:It is feasible and reliable to make a pathological diagnosis from frozen section of prostate targeted biopsy.

Prevention effect of low dose pre-irradiation on irradiation induced lung injury in mice and its possible mechanism / 中华放射医学与防护杂志

Objective:To evaluate the prevention effect of low dose pre-irradiation on irradiation-induced lung injury and its possible mechanism.Methods:Totally 320 6-week-old female C57BL/6j mice were divided into control (0 Gy), low-dose (0.5 Gy), high-dose (20 Gy) and low-dose pre-radiation(0.5 Gy+ 20 Gy)groups by the random number method, with 80 mice in each group. The mice in the low-dose and low-dose pre-irradiation groups were placed in the immobilization device under full consciousness and subjected to 0.5 Gy X-ray whole-body irradiation. 2 weeks later, the 0.5 Gy pre-irradiated mice were anesthetized and subjected to 20 Gy X-rays on chest, as the pre-radiation plus high dose radiation group. The mice in the control group were irradiated with mock irradiation (0 Gy). All mice were terminated at designed time points (24 h, 1 month, 3 months and 5 months) after completion of the irradiation schedule, with 20 mice/group at each time point. Then, lung tissues were taken from mice, and pathological changes were observed by hematoxylin-eosin (HE) staining and Masson′s trichrome staining. RT-qPCR and Western blot were used to detect the expressions of mRNAs and proteins of pulmonary fibrosis-related factors.Results:Pathological changes were observed in the lung tissues 1 month after a single high-dose 20 Gy irradiation, mainly including radiation pneumonitis and a small amount of collagen accumulation, which was more serious than low-dose pre-irradiation group, and these pathological changes became more severe when the time after irradiation increased. Meanwhile, the mRNA and protein levels of proSP-C and HOPX in the low-dose pre-irradiation group were higher than those in the high-dose group, except for proSP-C protein expression at 3 and 5 months post-irradiation. A more significant change was that the mRNA level of TGF-β1 in the high-dose group was 5.8-13.6 times higher than that in the other groups at 5 months after irradiation, as well as β-catenin mRNA ( t=4.22, 5.11, P<0.05). At the same time, in the early period (24 h and 1 month) post-irradiation, the level of vimentin protein in the low-dose pre-irradiation group was significantly higher than that in the high-dose group ( t=6.54, 4.28, P<0.05). Conclusions:When the mice were pre-irradiated with 0.5 Gy X-rays, an adaptive protective response was induced in lung tissues, resulting in the tolerance to subsequent high dose irradiation.

The adenosine analogue prodrug ATV006 is orally bioavailable and has potent preclinical efficacy against SARS-CoV-2 and its variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 pandemic, is rapidly evolving. Due to the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOC), including the currently most prevalent Delta variant, orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously we showed that adenosine analogue 69-0 (also known as GS-441524), possesses potent anti-SARS-CoV-2 activity. Herein, we report that esterification of the 5-hydroxyl moieties of 69-0 markedly improved the antiviral potency. The 5-hydroxyl-isobutyryl prodrug, ATV006, showed excellent oral bioavailability in rats and cynomolgus monkeys and potent antiviral efficacy against different VOCs of SARS-CoV-2 in cell culture and three mouse models. Oral administration of ATV006 significantly reduced viral loads, alleviated lung damage and rescued mice from death in the K18-hACE2 mouse model challenged with the Delta variant. Moreover, ATV006 showed broad antiviral efficacy against different mammal-infecting coronaviruses. These indicate that ATV006 represents a promising oral drug candidate against SARS-CoV-2 VOCs and other coronaviruses.

The diagnostic value of synthetic MRI quantitative parameters for prostate cancer / 中华放射学杂志

Objective:To investigate the diagnostic value of quantitative parameters of synthetic MRI in patients with prostate cancer (PCa).Methods:From April 2018 to April 2019, 25 PCa patients confirmed by whole-mount pathology were prospectively enrolled in Beijing Hospital. All patients underwent prostate MRI examinations including DWI and synthetic MRI. Four kinds of tissue types were identified in pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH) and prostatitis. According to the pathological results, quantitative parameters including ADC, T 1, T 2 and proton density (PD) values were measured on DWI and synthetic MRI. One-way analysis of variance or Kruskal-Wallis H test was performed to compare the difference of each parameter among PCa, SH or GH in the transitional zone (TZ). The difference of each parameter between PCa and prostatitis in the peripheral zone (PZ) was evaluated by using independent sample t test or Mann-Whitney U test. The diagnostic performance of each parameter in discriminating PCa from other benign conditions was evaluated by using ROC curve. Area under the curve (AUC) of each parameter was compared by using DeLong test. Results:The overall differences of T 1, T 2 PD and ADC values were statistically significant among PCa and other benign conditions. The T 1, T 2 and ADC values of PCa in the TZ were lower than those in the SH ( P=0.041, 0.030,<0.001) and GH (all P<0.001). The PD value of PCa in the TZ was lower than that in the GH ( P=0.040). The differences of T 1, T 2, PD and ADC values between PCa and prostatitis in the PZ were significant ( P<0.05). The AUC of ADC value (0.943) was higher than that of T 1 (0.691, P=0.001), PD (0.555, P=0.002) and T 2 (0.754, P=0.016) values in differentiating PCa from SH. For discriminating PCa and GH, T 1, T 2 and ADC showed similar AUC ( P>0.05), which were higher than AUC of PD value ( P=0.001). For discriminating PCa and prostatitis, T 1, T 2, PD and ADC values showed similar AUC ( P>0.05). Conclusions:Quantitative parameters of synthetic MRI were practical tools for discriminating PCa from other benign pathologies.

Study on the application of exercise stress echocardiography combined with layer-sepcific strain in patients with essential hypertension / 中华超声影像学杂志

Objective:To evaluate the diagnostic value of exercise stress echocardiography combined with left ventricular two-dimensional speckle tracking layer-specific strain technique in evaluating subclinical myocardial damage and reserve function in patients with hypertension.Methods:A total of 51 healthy subjects(control group) and 55 hypertensive patients (hypertension group) were enrolled in the treadmill exercise stress test in Sichuan Provincial People′s Hospital from October 2018 to January 2020. According to the European Guidelines for the Prevention and Treatment of Hypertension, the inclusion criteria for patients with hypertension were: blood pressure≥140/90 mmHg or who explicitly took antihypertensive drugs, and related cardiovascular diseases were excluded. The conventional parameters of resting and peak exercise, including left ventricular mass index, left ventricular end-diastolic volume index and left ventricular ejection fraction et al, were analyzed by speckle tracking software in two groups. According to the standard images in the resting and peak exercise, the endocardium /mid-myocardium /epicardium of left ventricular (three-, two-, four-chamber and global) longitudinal strain and circumferential strain (papillary muscle level) were compared respectively in two groups. The characteristics of strain differences and the systolic function reserve between the resting and peak exercise were evaluated.Results:There were significant differences in conventional ultrasound parameters between resting and peak exercise period in hypertension group, except E/A and e/a ratio (all P<0.05), and E/e value increased significantly(12.1±0.38) during peak exercise, indicating impaired diastolic reserve function. The longitudinal and circumferential layer-specific strain values from endocardial to epicardial were gradually decreased in both two groups. Compared with the control group, the resting longitudinal and circumferential endocardial strain values in hypertensive group were decreased, and the differences were more obvious at peak status, for instance global longitudinal endocardium strain at rest[control group (24.4±1.5)%, hypertension group (20.4±2.3)%], peak status[control group (30.8±2.8)%, hypertension group (22.8±2.9)%]( P<0.05). There were no significant differences of the partial layer-specific strain values between the peak exercise and resting status in hypertension group, while peak layer-specific strain of the control group were all significantly increased, suggesting that the left ventricular systolic reserve function of hypertension patients was lower than that of the control group. Conclusions:Left ventricular layer-specific strain can effectively evaluate the myocardial function in patients with hypertension, especially the endocardial strain can be used as an indicator parameter, and the peak exercise stress state is more sensitive. The systolic and diastolic reserve function of the left ventricle in patients with hypertension at the peak period are reduced to different degrees. Exercise stress echocardiography combined with left ventricular layer-specific strain technique can be used as a new method for detection of myocardial function impairment in patients with hypertension.

Risk factors of prostate cancer in men with PI-RADS 1-2 lesions by multiparametric MRI / 中华泌尿外科杂志

Objective:To evaluate the cancer detection rate in patients with multiparametric magnetic resonance imaging (mpMRI) PI-RADS 1-2 prior to initial biopsy, and analyze the risk factors of prostate cancer.Methods:A total of 196 patients undergoing initial prostate biopsy between July 2011 and June 2018 were retrospectively analyzed. According to ESUR PI-RADS system, the patients’ PI-RADS score was 1 and 2, with the mean age of 66.6±9.0 years, and the median PSA 7.44 ng/ml. Twenty-eight patients were enrolled with PSA<4 ng/ml but with abnormal directeral rectun examination. The rest 168 patients were enrolled with elevated PSA. According to the Epstein prostate risk classification criteria, clinically insignificant prostate cancer was defined as: PSA density ≤0.15 ng/ml 2, Gleason score≤6, less than 3 positive needles, <50% puncture length. If any of the above is not met, the diagnosis should be clinically significant prostate cancer(CsPCa). T test or Mann-Whitney U test were used for comparison between groups. Risk factors for diagnosis of prostate cancer and CsPCa were analyzed by chi square test(or Fisher’s exact probability method) and multivariate logistic regression analysis. Results:There were 42(21.4%) patients diagnosed with prostate cancer, 30(15.3%)patients were CsPCa. The negative predictive value of mpMRI was 78.6%(154/196)for prostate cancer overall, and 84.7%(166/196)for CsPCa. Patients with higher age and PSA density were associated with higher possibility of prostate cancer. Higher age, PSA level, PSA density, and lower PSA ratio were associated with higher possibility of CsPCa. Multivariate logistic regression analysis showed that PSA density>0.15 ng/ml 2( OR=2.94, 95% CI 1.45-5.95) was independent risk factor of prostate cancer.Ages over 70 years( OR=2.49, 95% CI 1.22-5.07), PSA ratio<0.2( OR=3.70, 95% CI 1.25-11.23), PSA density>0.15 ng/ml 2( OR=5.77, 95% CI 1.96-16.96) were independent risk factors of CsPCa ( P<0.05). Conclusions:The detection rate of prostate cancer was 21.4% in patients with elevated PSA or abnormal digital prostate examination but with PI-RADS score of 1-2. Higher age and PSA density were associated with higher risk of prostate cancer. The detection rate of CsPCa was 15.3%. Ages over 70 years, PSA ratio<0.2, PSA density>0.15 ng/ml 2 were independent risk factors of CsPCa.

Clinical pathological features of transition zone prostate cancer in the elderly / 中华老年医学杂志

Objective:To investigate the features of volume, distribution, grading and staging of prostate cancer(PCa)examined via whole-mount histopathology in transitional PCa.Methods:A total of 129 PCa patients undergone radical prostatectomy(RP)between July 2017 and March 2020 whose whole-mount prostate specimens were prepared after surgery were retrospectively studied.Pathological data on tumor locations, diameters and classification of the International Society of Urologic Pathology(ISUP), radiological data on regions of interest(ROI)and scores of the Prostate Imaging and Reporting Data System(PI-RADS v2)were recorded.The results of pathological whole-mount sections and prostate imaging were compared, and the characteristics and detection rates of lesions in different prostate regions were analyzed.Results:Of all 129 prostate specimens from RP, a total of 213 PCa lesions were detected through whole-mount histopathology.There were 21(9.9%)lesions involving both the peripheral zone(PZ)and the transition zone(TZ), with an average diameter of(2.82±0.71)cm.Of all lesions, 85(39.9%)involved PZ and 107(50.2%)involved TZ, with an average diameter of(1.36±0.81)cm and of(1.60±0.94)cm, respectively.The percentage of lesions involving TZ was higher than that lesions involving PZ, with larger diameters( P<0.05). Of 64 patients with complete MRI data, 105 PCa lesions were detected histopathologically by using whole mount sections, while 75 PCa lesions were detected by MRI, with a statistical difference( P<0.05). For lesions≥1.0 cm or lesions with an ISUP grade group≥2, the detection rate of MRI was lower in TZ lesions( P<0.05). Conclusions:PCa lesions within TZ account for a large proportion and have a relatively large tumor dimeter.PCa lesions within TZ are more likely to be missed in clinical examinations and on MRI, and clinicians should pay close attention during diagnosis and treatment.

Investigation of age-related white matter changes in adults brain using synthetic MRI: a preliminary study / 中华放射学杂志

Objective:To explore the relaxometry and volumetric characteristics of the adults brain at different ages using synthetic MRI.Methods:A total of 107 healthy volunteers in Beijing Hospital from November 2017 to August 2018 were enrolled in this study. According to the age, they were divided into 20-39 years group (29 persons), 40-59 years group (31 persons), 60-79 years group (30 years), and ≥80 years (17 persons). All participants underwent synthetic MRI. Volumetric parameters including white matter volume, white matter fraction, the T 1 and T 2 relaxometry of white matter were obtained. Nonlinear regression analysis was conducted between these parameters and age. ANOVA test was performed to assess the difference of parameters among different age groups. Pearson correlation coefficients between white matter volume and the white matter T 1 and T 2 values were also calculated. Results:White matter volume (male and female separately), white matter fraction, the T 1 and T 2 relaxometry of white matter followed a second order polynomial relationship with age [ R2 =0.67(male), 0.42(female), 0.44, 0.52, 0.25, P<0.001] and the white matter volume of males had the best goodness of fit. Significant differences were observed in white matter volume (male and female separately), white matter fraction, T 1 and T 2 relaxometry of the white matter among four age groups ( P<0.05). The white matter volume of male and female negatively linearly correlated with the T 1 [ r =-0.69(male), -0.73(female), P<0.001)] and T 2 [ r=-0.50(male), -0.49(female), P<0.001] of white matter. Conclusion:Synthetic MRI has demonstrated potential in detecting white matter alterations of relaxometry and volumetry during the aging process.

Bilateral filtering based sliding motion compensated 4D-CBCT: a simulation study / 中国辐射卫生

Objective This study reconstructed 4D-CBCT for fully automatic compensated sliding motion by incorporating the bilateral filtering into the Deformable Vector Field (DVF). Methods First, a motion compensated simultaneous algebraic reconstruction technique (Modified Simultaneous Algebra Reconstruction Technique, mSART) was used to generate a high quality reference phase by using all phase projection stogether with the initial 4D-DVFs, which were generated via Demons registration between 0% phase and each other phaseimage. The 4D-DVF was optimized by matching the forward projection of the deformed 0% phase with the measured projection of the target phase. The loss function’s DVF smoothing constrain term contained bilateral filtering kernel that contained: 1) an spatial domain Guassian kernel; 2) animage intensity domain Guassian kernel; and 3) a DVF domain Guassian kernel. By choosing suitable kernel variances, the sliding motion can be extracted. A non-linear conjugate gradient optimizer wasused. We validated the algorithm on a Non-Uniform Rotational B- spline based Cardiac-Torso (NCAT) phantom. Quantification was evaluated by: 1) the Root-Mean-Square-Error (RMSE) together with the Maximum-Error (MaxE); 2) the Dice coefficient of the extracted lung contour from the final reconstructed images and 3) the relative reconstruction error (RE) to evaluate the algorithm's performance. Results The motion trajectory's RMSE/MaxEare 0.796/1.02 mm for bilateral filtering reconstruction; and 2.704/4.08 mm for original reconstruction. Image content such a stherib position, the hearted gedefinition, the fibrous structures all had been better corrected with bilateral filtering. Conclusion We developed a bilateral filtering based fully automatic sliding motion compensated 4D-CBCT scheme. Digital phantom study confirmed the improved motion estimation and image reconstruction ability. It can be used as a 4D-CBCT image guidance tool for lung SBRTtreatment.

Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro

COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CLpro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root of Scutellaria baicalensis has been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts of S. baicalensis have exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredient compounds. We found that the ethanol extract of S. baicalensis inhibits SARS-CoV-2 3CLpro activity in vitro and the replication of SARS-CoV-2 in Vero cells with an EC50 of 0.74 g/ml. Among the major components of S. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CLpro activity with an IC50 of 0.39 M. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. Our study demonstrates that the extract of S. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors.

PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression and

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an glioma model, PCC0208017 showed robust anti-tumor activity, blood-brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma.