Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ² test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
Humans ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; China ; Nucleic Acids

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H₂O₂-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.

This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.
Alkaloids/pharmacology* ; Animals ; Antidepressive Agents/pharmacology* ; Depression/drug therapy* ; Disease Models, Animal ; Hippocampus ; Mice ; Mice, Inbred C57BL ; Stress, Psychological

OBJECTIVE: To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. METHODS: A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted. RESULTS: Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. CONCLUSIONS Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.
Brain Injuries ; Electroencephalography ; Humans ; Hypoglycemic Agents ; Infant, Newborn ; Neuroglobin ; blood ; Phosphopyruvate Hydratase

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Objective:To understand the impact of hierarchical medical system on the medical staff at all levels of medical institutions in the pilot areas,and their cognitive status and influencing factors for hierarchical medical sys-tem,for the purpose of providing scientific reference for improving the hierarchical medical system. Methods:435 of medical staffs were selected with the help of by stratified random sampling from different levels of medical institutions from 15 pilot areas and a questionnaire survey methodology was used in this study to gather views of the medical staffs. Results:It has been revealed that after the system is implemented,there were differences in the total monthly salary,performance pay ratio,workload and the relationship between doctors and patients at different levels of medi-cal institutions. The medical staff at all levels of medical institutions had a high degree of awareness of hierarchical medical system,and the cognition rate was 81.4%. Among them,tertiary hospitals,township hospitals,community health service centers,secondary hospitals;different department categories,job titles,performance pay ratio and sal-ary changes in the medical staff have different cognition of the grading. Conclusions:To further develop the key role of medical staff in the hierarchical medical system, strengthen the attention of secondary hospitals to enhance the service capacity of primary healthcare units at the same time,reform the pay system,mobilize the enthusiasm of med-ical institutions and medical staff,and promote the development of hierarchical treatment system.

OBJECTIVETo investigate the clinical value of gnome-wide chromosome microarray (CMA) technique in genetic etiological diagnosis of fetal cerebral ventriculomegaly.

METHODSA retrospective analysis was conducted in 109 women with singleton pregnancy, who were admitted in Nanfang Hospital with the diagnosis of cerebral ventriculomegaly in the fetuses by ultrasound between January, 2014 and December, 2016. Routine karyotype analysis and chromosome microarray analysis were performed to identify the chromosomal abnormalities in the fetuses.

RESULTSKaryotype analysis detected chromosomal abnormalities at a rate of 12.84% in these fetuses, significantly lower than the rate of 26.60% with CMA technique (P=0.004); the combined detection rate of the two techniques was 28.44%. In 17 cases, karyotype analysis yielded normal results while CMA microarray showed abnormalities with an extra abnormal detection rate of 15.60%. Among the 17 fetuses with chromosomal abnormalities, 6 had micro-deletion, 9 had micro-duplication, 1 had both micro-deletion and micro-duplication, and 1 had heterozygous loss of single parent diploid.

CONCLUSIONCMA technique can be used to detect abnormal chromosomal copy numbers in fetuses with cerebral ventriculomegaly to increase the detection rate of chromosomal abnormalities and facilitate prenatal consultation and prognostic evaluation.

For qualitative and quantitative analysis of related substances in clotrimazole cream, HPLC-Q-TOF spectrometer was used to analyze the fragmentation pathways and identify structures of the related substances. Five related substances named by BP (2018) were identified as impurity A ((2-chlorophenyl)-diphenylmethanol), impurity B (para-clotrimazole isomer), impurity E (2-chlorobenzophenone), impurity F (1-tritylimidazole) and impurity 4 (9-(2-chlorophenyl)-fluorene), respectively, by using impurity references matching and comparison with the literature data. Four related substances were detected in clotrimazole cream except impurity E, and 9-(2-chlorophenyl)-fluorene is the first identified impurity in this preparation. To establish an HPLC method for determination of the related substances in Clotrimazole Cream, the Agilent Poroshell Bonuns RP column was used (100 mm×4.6 mm, 2.7 μm) with UV detection at 215 nm. The mobile phase was acetonitrile-10 mmol·L^-1 dipotassium phosphate buffer (adjusted with phosphoric acid to pH of 5.80) with a flow rate of 1.0 mL·min^-1. Gradient elution was used. The column temperature was maintained at 40℃. A good linear behavior was achieved between component's concentrations and peak area for impurity A, B, E, F within the range of 0.20-10.02 μg·mL^-1, 0.20-10.00 μg·mL^-1, 0.20-10.10 μg·mL^-1, 0.10-5.01 μg·mL^-1 with the correlation coefficients were 0.999 7, 1.000 0, 1.000 0, 0.999 9, respectively. The average recoveries were 94.3%, 95.0%, 100.0%, 99.6% with RSDs were 2.8%, 2.2%, 1.1%, 2.7%, respectively (n=9). LOQ were 200.4, 200.0, 202.0, 100.2 ng·mL^-1, respectively. LOD were 57.25, 57.14, 57.71, 28.63 ng·mL^-1, respectively. The developed method was simple, rapid, accurate and effective for testing related substances in clotrimazole cream to control its quality, ensuring the safety of clinical medication.