Objective To discuss protein marks expressed differentially in placenta of Down's syndrome by means of proteomics. Methods We collected placenta of 18 patients(from March 2009 to December 2009 at Beijing Obstetrics and Gynecology Hospital), and divided them into two groups, one was 10 patients with fetal Down's syndrome, the other was normal pregnancies (normal chromosome) with other diseases. We separated proteins expressed in placentas of two groups by two-dimensional difference gel electrophoresis (2D-DIGE), and then analyzed the differential protein spots by software Decyder 6. 5, then,spots differentially expressed by 1.5 fold or more were analyzed by matrix assisted laser desorption ionizationtime of flight-mass spectrometry (MALDI-TOF-MS). In the end, the differential expressional levels of partially identified proteins were validated by western blot analysis. Results (1) Differential proteins of two groups protein spots of placentas separated by 2D-DIGE were analyzed by software Decyder 6. 5 (these colored lights scattered in the image were protein spots), a total of 56 spots out of 352 were differentially expressed (P<0. 05) in two groups. We analyzed 17 protein spots(12 protein spots were over-expressed and 5 protein spots were down-expressed) differentially expressed by 1.5 fold or more by MALDI-TOF-MS.(2) Protein matching after searching protein database, 17 protein spots turn out to be 10 proteins. Four kinds [superoxide dismutase 1 (SOD1), peroxiredoxin 6 (PRDX6), heat shock protein 27 (HSP27),endoplasmic reticulum protein 29 (ERP29)] of them were validated by western blot analysis, the group of fetal Down's syndrome were 0.74 ±0. 12,0.29 ±0. 10,0.53 ±0. 16,0.20 ±0. 09,the group of normal pregnancies were 0. 51 ±0. 08,0. 34 ± 0. 16,0. 18 ± 0. 07,0. 35 ± 0. 09, the results confirmed the observed changes in proteomics. Conclusions Compared with normal pregnancies, there were differential proteins expressed in placenta of Down's syndrome. This approach might provide new screening markers in use for prediction of Down's syndrome, however, further study should be done to make these 4 proteins (SOD1,HSP27, ERP29, PRDX6) be new screening markers.

Objective To study the relationship between serum erythropoietin(Epo)level and chemotherapy-induced hemoglobin(Hb)level in elderly patients with cancer. Methods　One hundred senile patients(aged≥60 years)with cancer and one hundred and seventy non-senile patients(aged＜60 years)with cancer were selected as aged group and control group,respectively.The serum Epo level was detected by enzyme-linked immunosorbent assay(ELISA). Results　(1)The average levels of the serum Epo in aged group and control group were(22.0±15.1)U/L and(30.4±21.8)U/L,respectively(t=1.2988,P＞0.05).A negative correlation was found between the levels of Epo and Hb in elder cancer patients(r=0.3700,P＜0.001).(2)The levels of serum Epo were(14.7±10.6)U/L,(20.2±9.0)U/L and(42.3±24.8)U/L in 55 cases with normal Hb level,22 cases with mild anemia and 23 cases with moderate to severe anemia,respectively(F=11.6886,P＜0.01).(3)The levels of Epo were(20.2±10.8)U/L,(45.2±39.1)U/L and(25.8±15.9)U/L before chemotherapy,after 4 treatment cycles and 2 treatment cycles respectively(F=4.5477,P＜0.01).The levels of Hb were(111.0±20.5)g/L,(96.8±16.6)g/L and(102.1±19.3)g/L before chemotherapy,after 4 treatment cycles and 2 treatment cycles respectively(F=4.0071,P＜0.01).Conelusions　There is no statistical difference in serum Epo level between senile patients with cancer and non-senile patients with cancer.but serum Epo levelis higher in patients with anemia than without anemia.There is a negative correlation between the levels of Epo and Hb.Chemotherapy can decrease the level of Hb and increase the serum 1evel of Epo in part of patients.The changes are correlated with the conditions of patients before chemotherapy and the time of chemotherapy.

BACKGROUND AND PURPOSE: Whether or not migraine can cause cumulative brain alterations due to frequent migraine-related nociceptive input in patients is largely unclear. The aim of this study was to characterize longitudinal changes in brain activity between repeated observations within a short time interval in a group of female migraine patients, using resting-state functional magnetic resonance imaging. METHODS: Nineteen patients and 20 healthy controls (HC) participated in the study. Regional homogeneity (ReHo) and functional interregional connectivity were assessed to determine the focal and global features of brain dysfunction in migraine. The relationship between changes in headache parameters and longitudinal brain alterations were also investigated. RESULTS: All patients reported that their headache activity increased over time. Abnormal ReHo changes in the patient group relative to the HC were found in the putamen, orbitofrontal cortex, secondary somatosensory cortex, brainstem, and thalamus. Moreover, these brain regions exhibited longitudinal ReHo changes at the 6-week follow-up examination. These headache activity changes were accompanied by disproportionately dysfunctional connectivity in the putamen in the migraine patients, as revealed by functional connectivity analysis, suggesting that the putamen plays an important role in integrating diverse information among other migraine-related brain regions. CONCLUSIONS: The results obtained in this study suggest that progressive brain aberrations in migraine progress as a result of increased headache attacks.
Brain Stem ; Brain* ; Female ; Follow-Up Studies ; Headache ; Humans ; Longitudinal Studies* ; Magnetic Resonance Imaging ; Migraine Disorders* ; Putamen ; Somatosensory Cortex ; Thalamus

Objective:To analyze the changing trend of intracerebral hemorrhage (ICH) incidence among residents with different characteristics during 9 years of comprehensive hypertension prevention and control (hypertension prevention and control) in Tengzhou from 2013 to 2021.Methods:From January 1, 2013 to December 31, 2021, the new ICH cases collected by the Center for Disease Control and Prevention in Tengzhou City were analyzed to calculate the incidence of ICH, and the trend of its distribution was analyzed among residents with different ages, sexes, and between urban and rural areas. The registered population information came from Tengzhou Public Security Bureau. Age and sex standardized incidence was calculated based on the 7th National Population Census in 2020. The Cochran-Armitage test was used to analyze the time and age trends of the incidence.Results:The overall ICH crude and standardized incidence in Tengzhou City decreased from 97.30/100 000 to 52.13/100 000 ( Z=-9.93, P<0.001) and 119.30/100 000 to 50.69/100 000 ( Z=-15.40, P<0.001) from 2013 to 2021, and both elevated to form a single peak in 2020, with 22.58% ( χ 2=24.02, P<0.001) and 18.09% ( χ 2=17.08, P<0.001) higher than in 2019, respectively. The trends in male and female incidence over the same period were similar to the overall trends, and the incidence was higher in males than in females in all years. The incidence of ICH increased with age in all years. The difference of increase in male incidence rate in 2020 was statistically significant in three age groups ≥45 years compared with 2019 (36.29%, 23.57% and 16.18%, respectively, χ 2=6.73, 4.65, 4.00, P<0.001). The incidence of ICH decreased by 70.07% and 36.23% ( Z=18.44, 5.22, P<0.001) in urban and rural areas respectively from 2013 to 2021, whereas increased by 34.15% ( χ 2=10.88, P<0.01) and 22.08% ( χ 2=18.63, P<0.001) in 2020 compared with 2019 separately. Conclusions:The incidence of ICH in Tengzhou from 2013 to 2021 showed a significant downward trend, with the decrease in the incidence of ICH in women exceeding that in men. The decrease in the incidence of ICH in urban areas exceeded that in rural areas, and male morbidity seemingly had a younger trend.

The pricing and reimbursement of orphan drugs are related to the accessibility of patients,and are of great significance to the prevention and guarantee of rare diseases.European countries have formed special standards and paths for health technology evaluation,and established special payment funds and diversified risk-sharing agreements,which have effectively improved the accessibility of orphan drugs.Based on this,it selected typical European countries to compare the orphan drug pricing and reimbursement methods.Then,it put forward some suggestions"building orphan drug health technology evaluation accelerated program,exploring the health of orphan drug classification security mechanism,and attaining supply incentives and development incentives through orphan drug pricing and adjustment",to optimize the basis for the orphan drug market access mechanism to provide reference.

Objective: To analyze the infection characteristics of patients in acute gastroenteritis outbreaks caused by noroviruses. Methods: Between April 2014 and March 2016, the clinical data and samples were collected from the patients in acute gastroenteritis outbreaks caused by noroviruses in Beijing. Noroviruses were detected and genotyped using real time RT-PCR, and the infection characteristics of norovirus gastroenteritis were analyzed using the descriptive epidemiological method. Results: A total of 1743 clinical diagnosed cases of norovirus gastroenteritis were collected, and children under 12 years old accounted for 77.68% (1354/1743). The detection rate of noroviruses was 73.98% (509/688). The detection rates of noroviruses in fecal, swab and vomitus samples were gradually decreased (χ²=67.798, P<0.001). Among these clinical diagnosed cases, vomiting was the most common symptom (93.98%), followed by abdominal pain (40.34%), diarrhea (30.35%) and fever (27.94%). The most common symptom of patients under 6 years old was vomiting(98.14%), whereas diarrhea was most common among over 18 years old patients (68.12%). With the increase of age of the patients, the incidence of vomiting was gradually decreased (χ²=100.913, P<0.001), whereas the incidence of diarrhea was gradually increased (χ²=261.164, P<0.001). There was no statistical difference in vomiting, diarrhea and abdominal pain symptoms between patients infected with genogroup Ⅰ and Ⅱ noroviruses, and patients infected with genogroup Ⅱ (34.49%, 149/432) had the higher incidence rate of fever than that of genogroup Ⅰ (18.18%, 14/77) (χ²=7.985, P<0.01). Conclusions Noroviruses mainly infected children under 12 years old in acute gastroentertis outbreaks. The most common symptom of patients with acute gastroenteritis caused by noroviruses was vomiting, and the incidences of vomiting and diarrhea were significantly correlated with age of the patients. Patients infected with genogroup Ⅱ had the higher incidence rate of fever than genogroup Ⅰ infection.

OBJECTIVE To systematically introduce the supply guarantee system of orphan drugs in South Korea， and to provide reference for improving the accessibility of orphan drugs in China. METHODS The basic characteristics and practical experience of supply guarantee system of orphan drugs in South Korea were summarized by studying the marketing incentive mechanism， reserve supply mechanism and emergency use mechanism. Then， based on the research on the current situation and existing problems of orphan drug supply in China， specific suggestions were put forward to improve the accessibility of orphan drugs in China. RESULTS & CONCLUSIONS South Korea has effectively improved the accessibility of orphan drugs through orphan drug identification channels and supporting incentive policies， relying on the reserve supply mechanism and the import route for emergency use. Therefore， it is suggested that China should guarantee the normal supply of orphan drugs from three aspects： improving the recognition and incentive policy of orphan drugs， building a full-time management department of orphan drugs， and optimizing the temporary import path.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.