Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

An improved U-shaped multi-lesion segmentation model,namely dense dilated attention pyramid UNet(DDAPNet),is proposed to overcome the difficulty in learning multi-scale features and address the issue of blurry boundaries in diabetic retinopathy(DR)segmentation task.DR images are treated with Patch processing to enhance the model's ability to capture local lesion features.After backbone feature extraction,a redesigned dense dilated attention pyramid module is introduced to expand the receptive field and address the issue of blurry lesion boundaries;and simultaneously,pyramid split attention module is used for feature enhancement;and then,the features output by the two modules are fused.Additionally,an improved residual attention module is embedded within skip connections to reduce interference from shallow redundant information.The joint validation on DDR dataset and real dataset from a specific hospital shows that compared with the original model,DDAPNet model improves the Dice similarity coefficient for segmentations of microaneurysms,hemorrhages,soft exudates and hard exudates by 4.31%,2.52%,3.39%and 4.29%,respectively,and increases mean intersection over union by 1.80%,2.24%,4.28%and 1.98%,respectively.The proposed model makes the segmentation of lesion edges smoother and more continuous,notably enhancing the segmentation performance for conditions like soft exudates in retinal lesions.

Objective:To explore the association between the spontaneous neural activity and memory function in depressive patients with different sleep quality.Methods:Totally 58 patients with depressive disorder and 58 gender-, age-, education-matched healthy controls (HC) completed 3.0 T MRI Scanning and clinical assessment including Wechsler memory scale (WMS), 24 Hamilton depression scale(HAMD-24) and Pittsburgh sleep quality index (PSQI). According to the score of PSQI, patients were divided into poor sleep quality group (PS, n=38) and good sleep quality group (GS, n=20). Amplitude of low frequency fluctuations (ALFF) were calculated and compared among three groups.Correlation analyses between the brain activity and the score of WMS were conducted as well. Results:Memory quotient of WMS showed differences among three groups( F=14.163, P<0.01), and the lowest score was found in patients with low sleep quality.The brain areas showed significant differences among three groups located in the left medial superior frontal gyrus (lmSFG, MNI: x=-10, y=30, z=58; K=56), right orbital inferior frontal gyrus (roIFG, MNI: x=26, y=20, z=-26; K=24) and left middle frontal gyrus (lMFG, MNI: x=-40 y=32, z=42; K=25) (voxel size P<0.001, cluster size P<0.05, GRF corrected). Compared with GS group, the ALFF of PS group showed significantly increased in the lmSFG, which was negatively correlated with memory quotient ( r=-0.327, P=0.045) and short term memory( r=-0.388, P=0.016). Compared with HC group, the ALFF of PS group showed increased in the lmSFG and lMFG, GS group showed increased ALFF in the roIFG. Conclusion:The impairment of memory function is more serious in patients with depression of low sleep quality, and the activity of frontal lobe is abnormally increased, which is related to memory function.Their association suggests that poor sleep quality in depressive patients may impair memory function by disrupting neural plasticity and synaptic pruning in the frontal lobes.

Objective To investigate the correlation between three single nucleotide polymorphisms of ABCG1 gene ( rs4148102,rs225445 and rs183436) and cerebral infarction of Li nationality in Hainan. Methods Totally 236 cases ( case group) of patients with cerebral infarction and 144 healthy controls (control group) of Li nationality who were treated in a hospital in Hainan province from January 2015 to June 2018 were selected. Genomic DNA from peripheral blood of patients in the two groups was extracted and gen-otype analysis was conducted using flight mass spectrometry. Snapstatus analysis software was used to analyze the association between haplotype and cerebral infarction,and Hardy-Weinberg equilibrium verification was performed. SPSS25. 0 was used to analyze the difference in genotype distribution and allele distribution. Re-sults The distribution frequencies of GG, AG, AA genotypes of rs4148102 in the case group ( 62. 7%, 25. 9%,11. 4%) and the control group(521. %,38. 2%,9. 7%) were significantly different (P<0. 05),and the occurrence frequencies of GG in the control group were significantly lower than those in the case group. The occurrence frequencies of TT,CT and CC of rs225445 were also statistically different between the two groups(36. 9%,41. 1%,22. 0% in case group,48. 6%,38. 2%,13. 2% in control group),and the occur-rence frequencies of CC in the control group was significantly lower than that in the case group. There were statistically significant differences in the frequencies of allele T and C of rs225445 and allele C and A of rs183436 between the two groups (P<0. 05). Conclusion Genotype GG of rs4148102 and genotype CC of rs225445 may be the susceptible factors of cerebral infarction in Li nationality in Hainan province.

EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.

Heat stroke (HS) is a life-threatening illness characterized by an altered level of consciousness with an elevated core body temperature 40 ℃, which may be further classified as exertional heat stroke (EHS) or classical heat stroke (CHS) according to the etiology of the condition. In recent years, the morbidity of EHS increases year by year. The severity and clinical outcome for an EHS casualty have a strong correlation with the area under the time and temperature curve for heat exposure. The early recognition and rapid cooling body core temperature ≤38.9 ℃ within 30 minutes of EHS results in the best clinical outcome and minimize severe multiple organ dysfunction and death for patients. Cold water immersion (CWI) is considered as an optimum cooling method for the reversal of hyperthermia in EHS. Some alternative modalities have also shown acceptable cooling rate, for example, the subjects immersed in a circulated water bath controlled below 20 ℃, tarp-assisted cooling with oscillation, body cooling unit, undressed, air-conditioned room, the whole body and large vessels placed ice packs, massaging the extremities; cold intravenous saline applied to dehydrated one. It is necessary to monitor body core temperature for hypothermia and/or recurrent hyperthermia, and to provide physical care for shivering, agitation, or concerns with the potential discomfort combativeness that may occur during cooling process. In this paper, pre-hospital recognition, care, monitoring and rapid cooling treatment measures of EHS have been reviewed to provide references for early identification of EHS and scientific, reasonable and effective cooling treatment.

Chronic heart failure(CHF)is the performance of end-stage cardiovascular disease and the leading cause of death in recent years.With the rapid development of medical care,the mortality rate of heart failure is still high.This is one in the two major challenges in the cardiovascular field in the 21st century.The new drug LCZ696 is a dual inhibitors of angiotensin receptor blockers(ARB)and neprilysin(NEP),which may lead to new hope for patients with heart failure.In order to determine the efficacy and safety of LCZ696 in the treatment of heart failure,foreign countries have carried out some large-scale trials,such as PARAMOUT, PARADIGM,TITRATION and so on.The results of these studies reflected the superiority of LCZ696 compared with enalapril,valsartan and other drugs in the treatment of chronic heart failure.ARB/antiotensin converting enzyme inhibitors(ACEI)targets the angiotensin receptor to dilate blood vessels and inhibits the sympathetic nerve,but their effects on sodium withdrawal and diuresis are weak.The sacubitril in LCZ696 prevents natriuretic peptide from degrading,strengthens the natriuretic diuretic and further expansion of blood vessels.Thereby it improves water and sodium retention and cardiac function.It can play a better synergistic role combined with valsartan.

OBJECTIVE:To investigate the role orientation of pharmacists in China,and to provide legislative suggestions for the formulation of pharmacist law in China. METHODS:Through literature study,the career and evolution process of pharmacists at home and abroad were traced. The obstacles of the role change of pharmacists in China were analyzed to put forward the enlight-enment to the legislation of pharmacist law in China. RESULTS & CONCLUSIONS:Pharmacists in the world had generally en-tered the stage of"taking medication safety of patients as the center"pharmaceutical care,but pharmacists in China were still in the transition stage from"taking drugs as the center"traditional pharmacy to"taking safe medication as the center"clinical phar-macy. The role cognition of pharmacists needed to be improved. Pharmaceutical care should be taken as the role orientation,and the scope of pharmacist law adjustment should be defined;the qualification admittance threshold of pharmacists should be im-proved with the goal of pharmaceutical care-oriented talents;Taking pharmaceutical care as the content,the rights and obligations of pharmacists should be defined. The legislation of pharmacists should be conducted in China to speed up the transformation of pharmacist's role into pharmaceutical care.

Objective To study the effects of Yunnan BaiYao on the expressions of c-fos and c-jun mRNA in HPDLFs and explore the potential mechanism that Yunnan BaiYao promotes the proliferation and differentiation of HPDLFs.Methods The HPDLFs tissue was obtained from the extracted healthy premolar.The HPDLFs used underwent four to six passages.Cells were divided into untreated group,positive control group and treated group.In treated group,HPDLFs were co-cultured with Yunnan BaiYao solution for 4h with gradient concentration.The expressions of c-fos and c-jun mRNA were determined by RT-PCR.Results The results showed that the expressions of c-fos and c-jun mRNA were up-regulated significantly in treated group compared with control group (P＜0.05) Conclusion Yunnna BaiYao can upregulate the expressions of c-los and C-jun mRNA in HPDLFs.Through upregulating the expressions of c-fos and c-jun mRNA in hPDLs,Yunnan BaiYao can promote proliferation and differentiation of ossification of HPDLFs to induce bone formation.

OBJECTIVETo investigate genetic polymorphisms of 12 X chromosome short tandem repeat (X-STR) loci in ethnic Hebei Han population using an Investigator Argus X-12 amplification kit.

METHODSDNA was extracted for 198 unrelated individuals (96 males and 102 females) and amplified with a fluorescence labeled multiplex PCR system. PCR products were separated and genotyped with capillary array electrophoresis.

RESULTSOnly DXS10103 and DXS10101 showed significant linkage disequilibrium at the 12 X-STR loci. One hundred and forty-eight alleles, including 22 off-ladder (OL) alleles, were observed at the 12 X-STR loci in the population. The heterozygosity and polymorphic information content (PIC) were 0.5074-0.9143 and 0.4377-0.9079, respectively. The power of discrimination (PD) was 0.5074-0.9143 in males and 0.6876-0.9863 in females. The mean exclusion chance was 0.4377-0.9079 in the trios cases and 0.2984-0.8373 in the duo cases, respectively.

CONCLUSIONThe Investigator Argus X12 amplification system is highly polymorphic in ethnic Han population from Hebei and is useful for personal identification and paternity testing.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; Chromosomes, Human, X ; genetics ; Female ; Genetics, Population ; Humans ; Male ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Genetic