A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

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.

【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.

Objective:To report a case of developmental epileptic encephalopathy caused by CACNA1E gene mutation and explore C Clinical phenotype and prognosis of 2069G>A (p.Gly690Asp) locus.Methods:The clinical data and follow-up of a case of developmental epilepsy related to CACNA1E gene mutation admitted to the Maternity And Children Health Hospital of Xiangtan City in September 2020 were summarized and analyzed.Results:The male patient, with delayed intellectual and motor development, sought medical attention and gradually developed seizures. The genetic results showed that the CACNA1E gene c. 2069G>A (p.Gly690Asp) was a newly discovered variant, and the parental site was a wild-type. Based on clinical manifestations, the diagnosis was a pathogenic variant.Conclusions:Developmental epileptic encephalopathy caused by mutations in the CACNA1E gene can have intellectual and motor impairments as the initial manifestation; Site C 2069G>A (p.Gly690Asp) presents with severe epilepsy and poor prognosis, with the possibility of brain atrophy. The combination of valproic acid and clonazepam may be effective in treating epilepsy.

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.

Objective:To evaluate the current status of the registered pediatric drug or vaccine clinical trials in China for the purpose of providing a reference for the development of pediatric clinical trials in China.Methods:We collected the data about registered pediatric clinical trials that were conducted from September 6, 2013(Mandatory registration start date) to September 6, 2019 (Cut-off date) at Chinadrugtrials.org.cn platform. The survey items included trial name and number, drug classification, sponsor′s information, current trial status, completion status, etc. The clinical trials were categorized by drug group (includes chemical medicine, traditional Chinese medicine and natural medicine, biological products) and by vaccine group.Results:During the six years 349 pediatric clinical trials were registered on the platform, including 162 pediatric drug trials and 187 vaccine trials. The numbers of chemical drugs and biological products registered in 2018 were 23 and 11, respectively, the highest in the history. The number of pediatric clinical trials of traditional Chinese medicine and natural medicine was 11 in 2014, but from 2015 to 2018 only 2 to 4 trials were registered each year. The overall completion rates of the registered drug and vaccine clinical trials were 22.8% (37/162) and 41.7%(78/187), respectively. Only 42 international multicenter pediatric clinical trial projects were registered on the platform. The numbers of drug and vaccine phase Ⅰ clinical trials were 4 and 46, respectively. Thirty-six pediatric endocrine system agent clinical trials were carried out, with the largest number of all the drug categories registered on the platform.Conclusions:In recent years the number of registered pediatric drug and vaccine clinical trials increased in China. However, the number is still very limited. It is urgent to further promote the development of pediatric clinical trials.

Objective To observe the effect of Shenmai injection on hemodynamics and serum inflammatory factors in patients with septic shock. Methods One hundred and fifty patients with septic shock admitted to Tianjin Fourth Center Hospital from August 2015 to March 2017 were enrolled and they were divided into a western medicine routine treatment group and an integrated traditional Chinese and western medicine treatment group according to the random number table method, 75 patients in each group. Both groups were given symptomatic treatment of basic western medicine, and the integrated traditional Chinese and western medicine treatment group was additionally given intravenous infusion (IV) of 30 mL Shenmai injection on the basis of conventional treatment, both groups were treated for consecutive 14 days. The changes in hemodynamic parameters, serum inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were observed before and after treatment in the two groups, and the clinical efficacies of the two groups were evaluated 14 days after treatment. Results After treatment in both groups, hemodynamic indexes were improved, heart rate (HR) was decreased, and mean arterial pressure (MAP), central venous pressure (CVP), cardiac output index (CI) and peripheral vascular resistance index (SVRI) were increased; after 14 days of treatment, HR in the integrated traditional Chinese and western medicine treatment group was significantly lower than that in the western medicine routine treatment group (bpm: 101.8±3.1 vs. 104.9±9.3), while MAP [mmHg (1 mmHg = 0.133 kPa): 71.2±4.3 vs. 67.3±3.5], CI (mL·s-1·m-2: 3.6±0.4 vs. 3.4±0.6) and SVRI (kPa·s·L-1·m-2:190.37±24.91 vs. 180.23±20.13) were significantly higher than those in the western medicine routine treatment group (all P < 0.05). TNF-α, IL-6 and IL-1β were decreased in both groups after treatment; after 14 days of treatment, the above indexes in the integrated traditional Chinese and western medicine treatment group were significantly lower than those in the western medicine routine treatment group [TNF-α (ng/L): 226.3±42.8 vs. 273.7±29.4, IL-6 (ng/L):223.7±31.2 vs. 259.3±51.3, and IL-1β (ng/L): 95.1±20.7 vs. 132.4±47.5]. The total clinical effective rate in the integrated traditional Chinese and western medicine treatment group was significantly higher than that in the western medicine routine treatment group [93.3% (70/75) vs. 54.7% (41/75), P < 0.05]. Conclusion Shenmai injection can improve hemodynamics and regulate inflammatory factors; the therapeutic effect for treatment of septic shock is significant.

Objective To analyze the effect of stratified nursing intervention based on aspiration risk assessment strategy in ICU mechanical ventilation patients. Methods Totally 156 patients with ICU mechanical ventilation admitted between January 2016 and December 2017 were selected as study subjects, and 78 patients were divided into treatment group and control group by random number table method. The control group was given routine nursing interventions for ICU patients undergoing mechanical ventilation, and the treatment group was combined with stratified nursing interventions based on aspiration risk assessment strategy. Compare the two groups of nurses'knowledge, attitude and practice of aspiration prevention, the complications of patient aspiration, patient satisfaction and other indicators. Results The scores of nurses′knowledge, attitude and practice of prevention of aspiration in the treatment group were (46.32 ± 3.24), (51.41 ± 3.56), and (49.36 ± 4.85), respectively, which were significantly higher than those of the control group (41.25 ± 5.32), (47.12 ± 5.45), (44.42 ± 5.46), The difference was statistically significant (t=4.815, 3.899, 4.002, P<0.05);The rate of aspiration, reflux, asphyxia, aspiration pneumonia in the treatment group was 7.69％ (6/78), 19.23％ (15/78), 1.28％ (1/78), 2.56％ (2/78), which were significantly lower than 29.49％ (23/78), 39.74％ (31/78),12.82％ (10/78),20.51％ (16/78) in the control group. The difference were statistically significant (χ2=7.892-12.309, P<0.05 or 0.01);Patient satisfaction 97.87％ (74/78) was significantly higher than the control group 83.33％ (65/78), The difference was statistically significant (χ2=5.347, P<0.05). Conclusion The stratified nursing intervention based on the aspiration risk assessment strategy can help develop nurses′ability in knowledge, attitude and practice of aspiration prevention, reduce the occurrence of complications such as aspiration, and improve patient satisfaction.

Objective To study the clinical events and risk factors of in stent restenosis (ISR) during the ＞1 year follow-up period after vertebral artery stenting.Methods Forty-six patients with 48 stents implanted from the Shaoxing No.2 Hospital between January 2010 and October 2016were divided into ISR group (n=8) and ISR-free group (n=38) or clinical events group (n=8)and clinical events-free group (n=38).The influencing factors for their long-term clinical outcome were analyzed after vertebral artery stenting.Results The mean stenosis length was (7.7 ± 4.6mm,the stenosis severity was 80.7％±14.2％,and the residual stenosis was 3.0％±8.4％ before stenting.The mean angiographic follow-up time was 31.6±20.8 months,during which ISR occurred in 8 patients (17.4％).The mean clinical follow-up time was 53.8±27.0 months,during which clinical events occurred in 8 patients (17.4％).Survival analysis showed that ISR usually occurred in the first 20 months and no clinical events occurred in 23 patiemts (50.0％) after vertebral artery stenting.The stenosis was significantly longer in ISR group than in ISR-free group (6.00±2.00 mm vs 2.76±4.14 mm,P=0.003).The diameter of stents was significantly shorter in clinical events group than in clinical events-free group (3.53±0.93 mm vs 4.18±0.67 mm,P=0.024).Conclusion The long-term clinical follow-up outcome is associated with the length and diameter of stents in patients after vertebral artery stenting.

Objective To investigate the homology of methicillin-resistant Stphylococcusaureus(MRSA)from the neonatal intensive care unit(NICU)of a children's hospital,and evaluate routes and preventive strategies of MRSA healthcare-associated infection(HAI). Methods MRSA strains from neonates and environment of NICU between October and December 2014 were collected,and strains were identified by VITEK-2 microbial analysis system and cefoxitin Kirby-Bauer method,homology of MRSA was analyzed by pulsed-field gel electrophoresis (PFGE ). Results A total of 6 MRSA strains were isolated from NICU between October and December 2014,3 of which (bed-58,70,and 100)were detected MRSA from specimens,MRSA were isolated from neonatal incubator and nurse (nasal swabs and hands)who cared for neonate at bed 58. 5 of 6 MRSA strains were homology,antimicrobial susceptibility testing result showed that No. 1-5 strains were resistant to clindamycin and amoxicillin/clavulanic acid,No. 6 strain was slightly different from No. 1-5 strains,No. 6 strain was susceptible to both clindamycin and amoxicillin/clavulanic acid. PFGE results showed that No. 1-5 strains were of the same type,No. 6 strain was a different type. Conclusion The main route of this MRSA transmission is contact transmission,especially through the hands of health care workers,identification and analysis of epidemic strains by PFGE technique is an effective measures to prevent HAI outbreak and perform epidemiological study.