OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Objective:To determine the diagnostic accuracy and prognosis of fetal congenital heart disease (CHD) detected by ultrasound at 11-13 weeks gestation.Methods:Fetuses at 11 to 13 + 6 weeks gestation in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and December 2022 were prospectively collected. Standrardized ultrasound was used to examine the fetuses. For the suspected fetal CHD, the section of cardiac ultrasound was improved as far as possible, and ultrasonic results, prenatal diagnosis, pathological anatomy and pregnancy outcome were followed up. Results:A total of 539 cases of CHD were detected in 72 242 fetuses with mixed risk in the first trimester, the incidence was 0.75% (539/72 242). The incidence of CHD in the fetuses with positive soft markers was 9.20% (287/3 118), and the incidence of multiple fetal malformations was 16.22% (235/1 449). The diagnostic accordance rate of complex CHD was 97.42%. For complex CHD, the sensitivity, specificity, false positive rate and false negative rate of first-trimester ultrasound were 90.41%, 99.98%, 0.02%, 9.59%. Combined with the results of this study, the abnormal section model of complex CHD was recommended. A total of 252 cases underwent staining chromosomal microarray or gene sequencing, of which 42.46% (107/252) were positive.Conclusions:Standardized ultrasound examination has a very high detection rate for fetal CHD in the first trimester. Transverse scanning of the heart can significantly improve the display of gray scale cardiac section, and reference to the cardiac section pattern map is beneficial to the early diagnosis of fetal CHD.

Objective To investigate the predictive value of vitamin D,sex hormones and their receptors in the development and regression of male patients with clinical isolated syndrome(CIS).Methods A total of 40 male CIS patients were included in the CIS group and 30 healthy subjects matched in age and long-term res-idence were included in the control group.The levels of vitamin D[1,25(OH)2D2 and 1,25(OH)2D3]inpe-ripheral blood of the included individuals and the first relapsed multiple sclerosis patients(MS group)were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry.The levels of testoster-one(T),progesterone(P),and estradiol(E2)in peripheral blood were detected by electrochemiluminescence.Estrogen receptor(ERα,ERβ),androgen receptor(AR)and vitamin D receptor(VDR)levels in lymphocyte supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Results After a median follow-up of 31.5 months,29 patients(72.5％)with CIS were converted to multiple sclerosis.Compared with pa-tients with non-recurrent CIS patients,patients with multiple sclerosis had a younger age of onset and were prone to positive oligoclonal bands.Compared with HC group,vitamin D levels were reduced in CIS patients,and the difference was statistically significant(P＜0.05).When CIS patients reverted to multiple sclerosis,se-rum levels of E2,ERα,and ERβ were elevated compared with those before relapse,and the levels of testosteroneand AR were decreased,and the difference was statistically significant(P＜0.05).Correlation analysis showed no correlation between peripheral blood levels of vitamin D,sex hormones and their receptors and EDSS in CIS patients.Conclusion Male CIS patients with younger onset age and positive oligoclonal bands are prone to transition to multiple sclerosis.The decrease of vitamin D level may be associated with the onset of male CIS.Vitamin D,sex hormones,and their receptors have no predictive value in the conversion of CIS to multiple sclerosis.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.

Objective:To assess the value of ultrasonography in the diagnosis of fetal isomerism syndrome in the first trimester.Methods:Sonographic features of 15 fetuses with isomerism syndrome diagnosed in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020 were reviewed. Ultrasonic characteristics in the first trimester were analyzed, and the ultrasonic characteristics of early mid-trimester and pathological anatomical results were combined for comparison.Results:There were 6 cases of left isomerism syndrome (LIS) and 9 cases of right isomerism syndrome (RIS) in the 15 fetues.Increased nuchal translucency(NT) (≥3.0 mm, 6 cases), reversed A wave in ductus venosus (10 cases), and atrio-ventricular valve regurgitation (14 cases) were found during the first trimester. There were 14 cases with abnormal visceral laterality. Of the 15 fetues, 14 cases with cardiac malformations, including 6 cases of functional single ventricle, 8 cases of complete atrioventricular septal defect (CAVSD), and 12 cases with great artery abnormalities. All of the 6 LIS cases had bradycardia, 3 cases had interruption of inferior vena cava (IVC). Six cases of RIS had juxtaposition of descending aorta and IVC, and 1 case of RIS had total anomalous pulmonary vein drainage. The major structural malformations were consistent with the early mid-trimester ultrasound examination or autopsy. Karyotype and chromosomal microarray were available in 12 cases and all were normal.Conclusions:Isomerism syndrome has high positive rate of fetal aneuploidies ultrasonographic marker, especially with the atrio-ventricular valve regurgitation, but the risk of chromosome abnormality is low. Ultrasound screening for fetal cardiac structural abnormalities is beneficial to the early diagnosis of isomerism syndrom in the first trimester.

Objective:To explore the feasibility and prognosis of prenatal ultrasonic diagnosis of fetal isolated vascular ring at 11-13 + 6 weeks. Methods:A total of 36 996 fetuses were selected to compare the results of ultrasound screening at 11-13 + 6 weeks and 20-24 weeks of pregnancy in Guangxi Maternity & Child Healthcare Hospital from January 2016 to January 2020, the reasons for missed diagnosis and misdiagnosis of fetal isolated vascular ring by ultrasonography in the first trimester were summarized. Results:Thirty-five cases were diagnosed as isolated vascular ring in the first trimester, including 19 cases right aortic arch combined with aberrant left subclavian artery with "U-shaped" vascular ring, 7 cases double aortic arch with "O-shaped" vascular ring, and 9 cases aberrant right subclavian artery with "C-shaped" vascular ring. While 155 cases were diagnosed as isolated vascular ring at 20-24 weeks of pregnancy, consisting of 18 cases of combined with aberrant left subclavian artery, 9 cases of double aortic arch, 126 cases of aberrant right subclavian artery and 2 cases of pulmonary artery sling, the diagnosis coincidence rates were 94.74%, 77.78%, 7.14%, 0(Kappa value were 0.97, 0.88, 0.13, 0). For the diagnosis of right aortic arch combined with aberrant left subclavian artery, double aortic arch and aberrant right subclavian artery in the first trimester, the specificities were 99.99%, 100%, 100%, the sensitivities were 100%, 77.78%, 7.14%, the false-positive rates were 0.01%, 0, 0, the false-negative rates were 0, 22.22%, 92.86%, and the Youden′s indices were 0.99, 0.78, 0.07.Conclusions:Right aortic arch combined with aberrant left subclavian artery and double aortic arch have high coincidence rate by ultrasonography in the first trimester, while the diagnostic coincidence rate of isolated aberrant right subclavian artery was low. Ultrasound screening for isolated vascular ring in the first trimester still needs ultrasound examination in the second trimester to exclude the minor cardiac malformations that are difficult to diagnose in the first trimester.

Objective    To provide recommendations for the management of intensive care unit patients without novel coronavirus disease 2019 (COVID-19). Methods    We set up a focus group urgently and identified five key clinical issues through discussion. Total 23 databases or websites including PubMed, National Guideline Clearing-House, Chinese Center for Disease Control and Prevention and so on were searched from construction of the library until February 28, 2020. After group discussion and collecting information, we used GRADE system to classify the evidence and give recommendations. Then we apply the recommendations to manage pediatric intensive care unit in the department of  critical care medicine in our hospital. Results    We searched 13 321 articles and finally identified 21 liteteratures. We discussed twice, and five recommendations were proposed: (1) Patients should wear medical surgical masks; (2) Family members are not allowed to visit the ward and video visitation are used; (3) It doesn’t need to increase the frequency of environmental disinfection; (4) We should provide proper health education about the disease to non-medical staff (workers, cleaners); (5) Medical staff do not need wear protective clothing. We used these recommendations in intensive care unit management for 35 days and there was no novel coronavirus infection in patients, medical staff or non-medical staff. Conclusion    The use of evidence-based medicine for emergency recommendation is helpful for the scientific and efficient management of wards, and is also suitable for the management of general intensive care units in emergent public health events.

Objective To investigate the potential risk factors for mild cognitive impairment (MCI) in the elderly population in the community, and to provide a basis for the primary prevention of MCI. Methods A cross-sectional study of elderly population in communities of Shanghai, China was conducted. A total of 368 subjects including both males and females, aged 65-80 years old, were selected to complete the mini-mental state examination (MMSE), basic information questionnaires, and physical examinations. Logistic regression analysis was used to analyze the potential risk factors of MCI. Results Of the 368 subjects participating in the study, 53 were found to have MCI and the prevalence rate was 14.4%. Univariate analysis found that older age, low education, no folic acid supplementation, stroke, osteoporosis and hyperlipidemia were risk factors of MCI. Multiple logistic regression analysis showed that advanced age [OR=1.146 (95%CI: 1.052-1.249)] and osteoporosis [OR=2.371 (95%CI: 1.042-5.396)] were the independent risk factors for MCI, while higher education [OR=0.073 (95%CI: 0.011-0.478)] was a protective factor. Age influenced all the aspects of MMSE scores (all P values <0.05). In addition, the analysis of the results suggested that subjects with regular folic acid supplementation got higher MMSE scores, especially in the aspect of language and praxis (P=0.002). On the contrary, patients with osteoporosis had lower attention and computing power scores (P=0.022). Conclusion The prevalence of MCI increased with age. Low education and osteoporosis may be the independent risk factors for MCI in the elderly population. Although no association was observed between folic acid supplementation and MCI, folic acid supplementation could improve the performance of language and praxis.

Objective　To explore the mechanism of apolipoprotein E （ApoE） affecting the expression of matrix metalloproteinase-9 （MMP-9） in astrocytes. Methods　（1） Astrocytes in wild-type （WT） and ApoE gene knockout （ApoE-/-） C57BL / 6J suckling mice were cultured in vitro；glial fibrillary acidic protein （GFAP） antibody were employed to identified the astrocytes. （2） Astrocytes from wild type WT and ApoE-/- C57BL/6J suckling mice were divided into blank control group（Control group），negative control group（NC group） and p65 gene knock down group（KD group）. No lentivirus was added to the Control group. The negative control lentivirus was added to the NC group，and the positive lentivirus that silended the p65 gene was added to the KD group. The nuclear factor-κB （NF-κB） p65 gene of astrocytes was silenced with siRNA lentivirus to inhibit NF-κB signal transduction. The expression of p65 protein was detected by Western blot，and MMP-9 and tumor necrosis factor-α（TNF-α） were detected by ELISA. （3）Add TNF-α to stimulate the astrocytes of each group for 24 hours，and the concentration of MMP-9 in each group of astrocytes before and after stimulation was measured by ELISA. Results　（1） The expression of NF-κB p65 protein and the concentrations of MMP-9 and TNF-α in the two astrocytes in the KD group were significantly lower than those in the Control group and the NC group （P<0.05），but those between the Control group and the NC group were no significant different（P>0.05）；（2） The concentration of MMP-9 and TNF-α of ApoE-/- astrocytes were higher than WT astrocytes in the Control group and NC groups （P<0.05），while those was no significant difference between ApoE-/- astrocytes and WT astrocytes in KD group （P>0.05）；（3） The concentrations of MMP-9 of the two types of astrocytes in Control group and NC group was increased after the stimulation of TNF-α（P<0.05），while the concentration of MMP-9 in the KD group had no significant change（P>0.05）. Conclusion　ApoE may affect the expression of MMP-9 in astrocytes through the TNF-α/NF-κB signaling pathway，and then affects the integrity of the blood-brain barrier.