Objective To explore the mechanism of abnormal metastable dynamics in Alzheimer disease(AD)using brain network dynamic model based on MRI.Methods Data of MR T1WI diffusion tensor imaging(DTI)and resting-state functional MRI(rs-fMRI)of 25 AD patients(AD group)38 mild cognitive impairment(MCI)patients(MCI group)and 37 healthy controls(HC group)in AD Neuroimaging Initiative(ADNI)database were collected.Based on abnormal brain structural connectivity and cortical atrophy characteristics of AD group the structural virtual injury brain network model was constructed and the mechanism of abnormal metastable dynamics in AD was explored.Results The abnormal functional connectivity of white matter in AD group was concentrated in visual network(VIS)default mode network(DMN)frontoparietal network(FPN)and limbic network(LIM).The overall metastable state of AD group in sensorimotor network(SMN)dorsal attention network(DAN)&ventral attention network(VAN)(i.e.attention network[AN])and DMN specific perturbation models were all significantly lower than that in HC group and MCI group respectively(all P＜0.001).In AD group local circuits abnormality could be seen in posterior right superior temporal gyrus precentral gyrus caudal anterior cingulate gyrus and isthmus of the cingulate gyrus leading to decrease in global metastability.The structural connection damage of DMN and AN as well as cortical atrophy of FPN had significant impact on metastable dynamics in AD patients.Conclusion Multimodal MRI brain network dynamic model revealed the core factors of mechanism of metastable dynamic decline in AD included DMN AN and FPN abnormalities.

Objective To explore the mechanism of abnormal metastable dynamics in Alzheimer disease(AD)using brain network dynamic model based on MRI.Methods Data of MR T1WI diffusion tensor imaging(DTI)and resting-state functional MRI(rs-fMRI)of 25 AD patients(AD group)38 mild cognitive impairment(MCI)patients(MCI group)and 37 healthy controls(HC group)in AD Neuroimaging Initiative(ADNI)database were collected.Based on abnormal brain structural connectivity and cortical atrophy characteristics of AD group the structural virtual injury brain network model was constructed and the mechanism of abnormal metastable dynamics in AD was explored.Results The abnormal functional connectivity of white matter in AD group was concentrated in visual network(VIS)default mode network(DMN)frontoparietal network(FPN)and limbic network(LIM).The overall metastable state of AD group in sensorimotor network(SMN)dorsal attention network(DAN)&ventral attention network(VAN)(i.e.attention network[AN])and DMN specific perturbation models were all significantly lower than that in HC group and MCI group respectively(all P＜0.001).In AD group local circuits abnormality could be seen in posterior right superior temporal gyrus precentral gyrus caudal anterior cingulate gyrus and isthmus of the cingulate gyrus leading to decrease in global metastability.The structural connection damage of DMN and AN as well as cortical atrophy of FPN had significant impact on metastable dynamics in AD patients.Conclusion Multimodal MRI brain network dynamic model revealed the core factors of mechanism of metastable dynamic decline in AD included DMN AN and FPN abnormalities.

Objective To predict the structure and antigenic epitope of the Strongyloides stercoralis serine protease inhibitor 1 (Ss-SRPN-1) protein using bioinformatics tools, and to construct prokaryotic expression plasmids for expression of recombinant Ss-SRPN-1 protein, so as to provide the basis for unraveling the function of the Ss-SRPN-1 protein. Methods The amino acid sequence of the Ss-SRPN-1 protein was downloaded from the NCBI database, and the physicochemical properties, structure and antigenic epitopes of the Ss-SRPN-1 protein were predicted using bioinformatics tools, including ExPASy, SWISS-MODEL and Protean. Primers were designed according to the nucleotide sequences of Ss-SRPN-1, and the Ss-SRPN-1 gene was amplified, cloned and sequenced with genomic DNA extracted from the infective third-stage larvae of S. stercoralis as a template. The Ss-SRPN-1 protein sequence was cloned into the pET28a (+) expression vector and transformed into Escherichia coli BL21 (DE) cells for induction of the recombinant Ss-SRPN-1 protein expression. The recombinant Ss-SRPN-1 protein was then purified and identified using Western blotting and mass spectrometry. Results Bioinformatics analysis showed that the Ss-SRPN-1 protein, which was composed of 372 amino acids and had a molecular formula of C₁₉₄₈H₃₀₄₆N₄₈₈O₅₇₅S₁₆, was a stable hydrophilic protein, and the subcellular localization of the protein was predicted to be extracellular. The Ss-SRPN-1 protein was predicted to contain 11 dominant B-cell antigenic epitopes and 20 T-cell antigenic epitopes. The Ss-SRPN-1 gene with a length of 1 119 bp was successfully amplified, and the recombinant plasmid pET28a (+)/Ss-SRPN-1 was constructed and transformed into E. coli BL21(DE) cells. The expressed recombinant Ss-SRPN-1 protein had a molecular weight of approximately 43 kDa, and was characterized as a Ss-SRPN-1 protein. Conclusions The recombinant Ss-SRPN-1 protein has been expressed successfully, and this recombinant protein may be a potential vaccine candidate against strongyloidiasis.

Objective To investigate the dynamic expression of cluster of differentiation 47 (CD47) and its ligands signaling regulatory protein α (SIRPα) and thrombospondin-1 (TSP-1) in mice infected with Toxoplasma gondii in the second and third trimesters.. Methods C57BL/6J mice (6 to 8 weeks old) were used for modeling T. gondii infection in the first trimester, and the pregnant mice were randomly divided into the normal control and infection groups, of 10 mice in each group. Pregnant mice in the infection group were intraperitoneally injected with 150 T. gondii tachyzoites on gestational day (Gd) 6.5, while pregnant mice in the normal control group were intraperitoneally injected with the same volume of physiological saline at the same time. The uterine and placental specimens were collected from all pregnant mice on Gd12.5 and Gd18.5, and the pregnant outcomes were recorded. The pathological damages of mouse uterine and placental specimens were observed using hematoxylin-eosin (HE) staining on Gd12.5 and Gd18.5. The relative expression of CD47, SIRPα, TSP-1, surface antigen 1 (SAG1), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4 and IL-13 mRNA was quantified in mouse uterine and placental specimens using real-time fluorescence quantitative PCR (qPCR) assay, and the CD47, SIRPα, TSP-1 expression was determined in mouse uterine and placental specimens using immunohistochemical staining. Results As compared with those in the normal control group, the pregnant mice in the infection group showed back arching, bristling, trembling and listlessness during pregnancy, and several mice presented virginal bleeding and abortion. Pathological examinations showed inflammatory cell infiltration, congestion and necrosis in uterine and placental specimens of pregnant mice in the infection group, a higher abortion rate of pregnant mice was seen in the infection group than in the normal control group on Gd12.5 (χ² = 20.405, P < 0.001) and Gd18.5 (χ² = 28.644, P < 0.001). qPCR assay showed significant differences in the expression of CD47, SIRPα, TSP-1, SAG1, INF-γ, IL-2, IL-4 and IL-13 genes in mouse placental specimens between the normal control and infection groups on Gd12.5 and Gd18.5 [F′ (F) = 37.511, 29.337, 97.343, 53.755, 67.188, 21.145, 8.658 and 13.930, all P values < 0.001]. Higher CD47, SIRPα and TSP-1 gene expression was quantified in mouse placental specimens in the infection group than in the normal control group on Gd12.5 (all P values < 0.01), and lower CD47, SIRPα and TSP-1 gene expression was quantified in the infection group than in the normal control group on Gd18.5 (all P values < 0.001), while higher SAG1 gene expression was detected in placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01). In addition, higher INF-γ and IL-2 expression and lower IL-4 and IL-13 expression was detected in mouse placental specimens in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001), and there were significant differences in the CD47, SIRPα, TSP-1, SAG1, INF-γ, IL-2, IL-4 and IL-13 gene expression in uterine specimens of pregnant mice between the normal control and infection groups on Gd12.5 and Gd18.5 [H(F′ and F) = 14.951, 25.977, 18.711, 48.595, 39.318, 14.248 and 15.468, all P values < 0.01], and higher CD47 and TSP-1 expression was detected in mouse uterine specimens in the infection group than in the control group on Gd12.5 and Gd18.5 (all P values < 0.01); however, no significant difference was found in the SIRPα expression (P > 0.05). Higher SAG1 expression was detected in uterine specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01), and higher INF-γ and IL-2 gene expression and lower IL-4 and IL-13 gene expression was found in the placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001). Spearman correlation analysis showed that the CD47 gene expression correlated positively with IFN-γ (r_s = 0.735, P < 0.05) and IL-2 (r_s = 0.655, P < 0.05) and negatively with IL-4 (r_s = −0.689, P < 0.05) and IL-13 expression (r_s = −0.795, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd12.5, and the CD47 gene expression correlated negatively with IFN-γ (r_s = −0.745, P < 0.05) and IL-2 expression (r_s = −0.816, P < 0.05) and positively with IL-4 (r_s = 0.704, P < 0.05) and IL-13 (r_s = 0.802, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd18.5. Immunohistochemical staining showed mild CD47, SIRPα and TSP-1 expression in uterine and placental specimens of pregnant mice in the normal control group on Gd12.5 and Gd18.5, strong CD47, SIRPα and TSP-1 expression in the placental specimens of pregnant mice in the infection group on Gd12.5 and strong CD47 and TSP-1 expression in the uterine specimens of pregnant mice in the infection group on Gd12.5. Conclusions T. gondii infection in the first trimester may cause abnormal expression of CD47 and its ligands SIRPα and TSP-1 in the maternal-fetal interface of pregnant mice in the second and third trimesters, which may be associated with the immune escape of T. gondii at the maternal-fetal interface.

Objective: To explore effect of intensive intervention for improving the referral rate of children with visual refractive disorders, and to provide a reference for myopia prevention and control of children and adolescents. Methods: A total of 4 464 preschool children were selected from Zhuanqiao county, Minghang district in Shanghai for the eyesight investigation during April to June in 2019. Stratified random cluster sampling method was used to divide 1 724 children into intervention group and (896) control group (828) depending on the type of kindergartens. The intervention group was provied with an intensive intervention, including children s vision health assessment, parental self management guidance for children s eye care, and community based eye care services, while the control group carried out routine intervention measures. Results: In 2019, the incidence of visual and primary refractive screen abnormalities in preschoolers of Zhuanqiao community was 38.62%. The incidence of naked eye vision abnormalities was 4.40%, the incidence of myopia risk group, hyperopia risk group and astigmatism risk group was 37.10%, 2.20%, and 6.10 %, respectively. After the intervention, the referral rate of the intervention group (68.75%) was significantly higher than that of the control group (17.15%)( χ 2=465.09, P <0.01). The differences between two groups were statistically significant in choosing the hospital for treatment ( χ 2=10.01, 51.51, 15.40, 27.79, 19.96, 24.24, P <0.01). Conclusion The vision and refractive status of preschoolers worths further attention. Intensive intervention can improve the referral rate for children with screened vision abnormalities, which facilitates the prevention and early diagnosis of vision problems among preschoolers.

Objective:To investigate gender measurement invariance of the Perceived Social Support Scale(PSSS)in people aged 50 years and older.Methods:A total of 1013 adults(50-96 years old)in Beijing, Hunan and Shandong were tested by using PSSS.The measurement invariance of PSSS between middle-aged and elderly males and females was analyzed.Differences in PSSS total scores and subscale scores between males and females were examined.Results:The equivalence test results of each item in the questionnaire met the requirements of the metrology(△CFI≥0.010, △TLI≥0.010, △RSMEA≤0.015), indicating that the hypotheses of morphological equivalence, weak equivalence, strong equivalence and strict equivalence of PSSS were all valid in the middle-aged and elderly population regardless of gender.In addition, middle-aged and elderly females had higher scores in family support, support from friends, support from other people and perceived social support than their male counterparts( P<0.05). Conclusions:PSSS has cross-gender equivalence in middle-aged and elderly people.Thus, differences in PSSS can reflect the perceived social support level in middle-aged and elderly people of different genders.

A 53-year-old female patient with multiple metastases of colon cancer was treated with regorafenib 120 mg/d orally (21 days of medication and 7 days of withdrawal was defined as 1 cycle). On the 7th day of regorafenib treatment, the patient developed intermittent pain in the right upper abdomen and waist, which was gradually aggravated. After 20 days of waist pain, renal ultrasound and abdominal CT examination showed a right perirenal subcapsular hematoma and laboratory tests showed hemoglobin 99 g/L and normal coagulation function. Spontaneous perinephric hematoma due to regorafenib was considered. Regorafenib was discontinued, the patient was instructed to stay in bed, and hemostasis and rehydration therapy was given. After 11 days of drug withdrawal, the patient′s lumbar pain was improved and hemoglobin returned to 102 g/L. After 2 months of drug withdrawal, abdominal ultrasound showed that the right perirenal hematoma was reduced and hemoglobin returned to normal.

A 53-year-old female patient with multiple metastases of colon cancer was treated with regorafenib 120 mg/d orally (21 days of medication and 7 days of withdrawal was defined as 1 cycle). On the 7th day of regorafenib treatment, the patient developed intermittent pain in the right upper abdomen and waist, which was gradually aggravated. After 20 days of waist pain, renal ultrasound and abdominal CT examination showed a right perirenal subcapsular hematoma and laboratory tests showed hemoglobin 99 g/L and normal coagulation function. Spontaneous perinephric hematoma due to regorafenib was considered. Regorafenib was discontinued, the patient was instructed to stay in bed, and hemostasis and rehydration therapy was given. After 11 days of drug withdrawal, the patient′s lumbar pain was improved and hemoglobin returned to 102 g/L. After 2 months of drug withdrawal, abdominal ultrasound showed that the right perirenal hematoma was reduced and hemoglobin returned to normal.

OBJECTIVE：To study the effects of berberine on mic e macrophage polarization based on TLR 4-MyD88-NF-κB signaling pathway. METHODS ：Using mice RAW 264.7 macrophage as the object ，atorvastatin calcium as positive control ， inflammatory cell model was induced by lipopolysaccharide （LPS）；ELISA method was used to detect the contents of TNF-α，IL-6 and NF-κB in cell culture medium after treated with low，medium and high doses of berberine （5，10，20 μmol/L）for 24 h. The real-time fluorescence quantitative PCR was conducted to determine the mRNA expression of TLR 4 and MyD 88 in cells. Western blotting assay was used to detect the protein expression of TLR 4，MyD88，iNOS and CD 206 in cells. RESULTS ：Compared with blank control group ，the contents of TNF-α，IL-6 and NF-κB in cell culture medium，mRNA expression of TLR 4 and MyD 88， protein expression of TLR 4，MyD88 and iNOS in cells were increased significantly in LPS induction group （P＜0.05）. Compared with LPS induction group ，the contents of TNF-α and IL-6，mRNA and protein expression of TLR 4 and MyD 88 in atorvastatin calcium group ，berberine medium-dose and high-dose groupsas well as the content of NF-κ B and protein expression of iNOS in administration groups were decreased significantly ， while the content of NF-κB in berberine high-dose group was significantly lower than atorvastatin calcium group （P＜0.05）. The protein expressions of CD206 in atorvastatin calcium group and berberine high-dose group were increased significantly ，while the protein expression of CD 206 in berberine high-dose group was significantly higher than atorvastatin calcium group （P＜0.05）. CONCLUSIONS ：Different doses of berberine can intervene in mice macrophage polarization to different extents ，the mechanism of which may be associated with the regulation of TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE： To systematically evaluate the difference in therapeutic efficacy， safety and cardiac function of Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment after percutaneous coronary intervention （PCI）， and to provide evidence-based reference for clinical drug use. METHODS： Retrieved from Cochrane library， PubMed， Embase， CNKI， Wanfang database and Chinese sci-tech periodicals database， RCTs about different Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment （trial group） versus routine treatment （control group） after PCI were collected. After screening the literature and extracting the data， the quality of the included studies was evaluated by modified Jadad scale. Bayesian network Meta- analysis was performed by using Stata 14.0 software and Markov Chain-Monte Carlo method. RESULTS： A total of 15 RCTs involving 1 364 patients were included， involving Salvia miltiorrhiza injection， Puerarin injection， Yiqi fumai injection， Xuebijing injection， Shenfu injection， Shuxuetong injection， Salvia miltiorrhiza and ligustrazine injection， Rhodiola wallichiana injection， Danhong injection. Results of Meta-analysis showed that in the aspect of improving total response rate of ECG， 8 kinds of intervention measures were involved；compared with control group， 7 kinds of intervention measures could improve the total response rate of ECG of trial group except for Shenfu injection （P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza injection＞Puerarin injection＞Shenfu injection＞S. miltiorrhiza and ligustrazine injection＞Shuxuetong injection＞R. wallichiana injection＞ Danhong injection＞routine treatment. In terms of reducing adverse cardiovascular events （MACE） incidence，8 kinds of intervention measures were involved； compared with control group， 7 kinds of intervention measures could reduce the MACE incidence of trial group except for Puerarin injection （P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection＞Danhong injection＞Xuebijing injection＞Shuxuetong injection＞S. miltiorrhiza injection＞R. wallichiana injection＞ Puerarin injection＞routine treatment. In terms of improving left ventricular ejection fraction （LVEF） after treatment， 8 kinds of intervention measures were involved； compared with control group， 7 intervention measures could significantly improve LVEF after treatment of trial group except for R. wallichiana injection (P＞0.05）； network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection＞Yiqi fumai injection＞Danhong injection＞Shenfu injection＞S. miltiorrhiza injection＞Shuxuetong injection＞R. wallichiana injection＞routine treatment. CONCLUSIONS： Compared with routine treatment， S. miltiorrhiza injection is the best in improving total response rate of ECG； S. miltiorrhiza and ligustrazine injection is the best in reducing MACE incidence and improving LVEF after treatment.