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 investigate the effects of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in coronary arteriosclerosis(AS)on the migration of stem cell antigen-1(Scal-1)and Nanog positive cells migration.Methods Ten atherosclerotic model mice and 10 normal mice were taken respectively,and the fresh hearts of the two groups were taken out,OCT embedding,frozen sections,HE staining and oil red O staining were performed respectively to observe the pathological changes of coronary arteries;Using immunohistochemical staining techniques,the expression changes of TNF-α,IL-6,Scal-1,and Nanog in the coronary artery wall were observed under light microscope.The ventricular tissue of 20 1-week-old mice was excised.Primary Scal-1 and Nanog positive cells were extracted using density gradient centrifugation,and these cells were purified and cultured.Immunofluorescence technology was used to identify the purity of Scal-1 and Nanog positive cells.Transwell migration experiments on passage 1(P1)cells was performed to observe the effects of different concentrations of inflammatory factors on the migration of Scal-1 and Nanog positive cells.Results The blood lipid test showed that the total cholesterol,triglycerides,and low-density lipoprotein cholesterol of the model mice were significantly higher than those of the normal control group.Histological staining showed that all the mouse models had obvious coronary atherosclerosis plaque.Immunohistochemical staining results showed that the inflammatory factor TNF-α and IL-6 in atherosclerosis region were strong positive expression,while Scal-1 and Nanog positive cells in atherosclerotic plaques increased,compared to the normal group.The positive rate of Scal-1 in P1 generation cells was about 80％,The positive rate of Nanog was approximately 91％.The Transwell experiment showed that IL-6 had no effect on cell migration at low concentrations,but had an inhibitory effect on cell migration at high concentrations;Low concentrations TNF-α promoted cell migration with 0.5 μg/L TNF-α showing the most significant effection cell migration,and exhibiting inhibitory effects inhibit at high concentrations.Conclusion TNF-α and IL-6 inflammatory factors,Scal-1 and Nanog positive cells are all involved in the occurrence and development of AS,and the appropriate concentration of inflammatory factors can enhance the migration of stem cells to the coronary atherosclerosis region.

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.
Powders ; Solubility ; Technology, Pharmaceutical ; Technology ; Plant Extracts ; Particle Size

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d_0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m²·g^-1 and 12.512 m²·g^-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m^-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m^-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.

Aim To study the mechanism of the ethanol extract from Leucopaxillus giganteus (LGEE) in treating breast cancer based on network pharmacology and molecular experimental validation. Methods Some chromatographic methods were used to isolate the chemical constituents of LGEE, and their structures were elucidated based on spectral data. The antitumor activities of LGEE were determined by MTT assay. The predicted targets of LGEE were selected by TCMSP and Pharmmaper, and Genecards database was used to screen the targets. GO and KEGG analysis of target genes were performed. Molecular docking was used to test the binding of active components to core targets. Western blotting was used to validate the regulating function of chlorogenic acid on CHEK2 and CASP3 targets of MDA-MB-231 cells. Results Thirteen compounds were identified including clitocine, chlorogenic acid and so on. LGEE displayed anticancer activities against MDA-MB-231 with the inhibition percent (87. 35 ± 1. 55)%, at the concentration of 200 mg· L

AIM: To investigate the protective effect of salvianolic acid B on retina and its influence on angiogenesis in retinal vein occlusion(RVO)injured rats.METHODS: SD rats were randomly divided into control group, model group and salvianolic acid B group, with 10 rats in each group. In addition to the control group, rats in model group and salvianolic acid B group were induced RVO by Bengal red combined with laser photodynamic method. The rats in salvianolic acid B group were intraperitoneally injected with salvianolic acid B 50 mg/(kg·d), while the rats in control group and model group were only given the same amount of normal saline for 21 consecutive days. Fundus fluorescein angiography(FFA)was used to observe the retinal vein structure before and after administration. HE staining was used to observe the pathological changes of rat retina. The retinal function of rats was evaluated by electroretinogram(ERG). The fluorescence expression of vascular endothelial growth factor A(VEGFA)in retina of rats in each group was detected by immunofluorescence staining. The relative expression of HIF-1α, STAT3, p-STAT3 and VEGFA proteins in retinal tissue were detected by Western blotting.RESULTS: Compared with the control group, the blood flow at the retinal obstruction in the model group was recanalized, and the effective collateral circulation was abundant, but the shape was irregular, and there was fluorescence leakage. In salvianolic acid B group, the retinal vein circulation recovered, the shape became regular gradually, and the collateral vessels decreased. The retina of the model group and salvianolic acid B group showed different degrees of pathological damage. At the same time, the amplitude of ERG a wave and b wave, the thickness of retinal total layer(RTL), inner nuclear layer(INL)and outer nuclear layer(ONL)decreased, the fluorescence intensity of VEGFA enhanced, and the relative expression of HIF-1α, p-STAT3 and VEGFA protein increased(P<0.05). Compared with the model group, the retinal histopathological damage of salvianolic acid B rats was alleviated, the amplitude of ERG a-wave and b-wave, the thickness of RTL, INL and ONL were increased, the fluorescence intensity of VEGFA was weakened, and the relative expression of HIF-1α, p-STAT3 and VEGFA proteins was decreased(P<0.05).CONCLUSION: Salvianolic acid B can alleviate the retinal histopathological injury and improve retinal function in RVO rats, which may be related to inhibiting the activation of HIF-1α/STAT3/VEGFA pathway and reducing angiogenesis.

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P<0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P<0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P>0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P<0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P>0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P<0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P>0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P<0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

Objective To investigate the structural distribution features and mechanism of elastic fibers and collagen fibers in ventricular interstitium of aged rats. Methods Five young SD rats (24 weeks) and five old SD rats (104 weeks) were used,and their cardiac function was examined by echocardiography. Modified Weigert elastic fiber staining, immunohistochemistry, immunofluorescence and Western blotting techniques were used to detect the expression changes of type I and IH collagen fibers and their proteins, elastic fibers and their proteins, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 2 (TIMP-2), respectively. Results The type I and type IH collagen in the ventricular interstitium of aged rats was very sufficient and wrapped around the cardiomyocytes. Compared with the young rats, the content of collagen protein in the ventricular interstitium of the aged rats significantly increased (P<0. 05). Elastic fibers in the ventricular interstitium of the aged rats were and widely distributed. Compared with the young rats, the number of elastic fibers and the level of elastin in the ventricular interstitium of the aged rats significantly decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in ventricular muscle of aged rats increased, and the)' were correlated with the level of elastin. The level of TIMP-2 in ventricular muscle of aged rats decreased with age. Conclusion The number of collagen fibers and elastic fibers in ventricular interstitium of aged rats is fluctuated with each other. With the increase of age, the contents of TIMP-2 and elastic fibers in the ventricular interstitium gradually decreased, and the ratio of collagen fibers to elastic fibers is out of balance.

AIM: To explore the efficacy of Danshen injection iontophoresis in the treatment of retinal vein occlusion(RVO).METHODS: The clinical data of 90 patients(90 eyes)with RVO treated in our hospital from January 2020 to December 2021 were analyzed retrospectively, and they were divided into control group and observation group according to treatment methods. A total of 38 patients(38 eyes)in the control group were treated with intravenous Xueshuantong+oral compound Xueshuantong capsule+enteric-coated aspirin, and 52 patients(52 eyes)in the observation group were treated with Danshen injection iontophoresis on this basis. The treatment time of the two groups was 3mo. The clinical efficacy, best corrected visual acuity, retinal condition and hemorheological indexes(whole blood low shear viscosity, fibrinogen)were compared between the two groups before and after treatment.RESULTS: The total effective rate of the observation group was significantly higher than that in the control group(87% vs 58%,P<0.05)at 3mo after treatment. The best corrected visual acuity in both groups was better than that before treatment, and the observation group was better than the control group(all P<0.05).The circulation time of retinal vein, the relative diameter of retinal vein and the relative area of retinal hemorrhage in the observation group were lower than those before treatment,and the observation group was lower than the control group(all P<0.05). The whole blood low shear viscosity and fibrinogen levels in the two groups were lower than those before treatment, and the observation group was lower than those in the control group(all P<0.05).CONCLUSION: Danshen injection iontophoresis is effective in the treatment of patients with RVO, which can effectively improve the visual acuity, treat fundus lesions and improve the abnormal blood flow.

Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.
Adenocarcinoma/pathology* ; Appendiceal Neoplasms/surgery* ; Carcinoid Tumor/surgery* ; Chromogranin A ; Female ; Goblet Cells/pathology* ; Humans ; Male ; Neuroendocrine Tumors/pathology* ; Repressor Proteins ; Synaptophysin