Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Left ventricular assist devices (LVAD) are increasingly used in patients with end-stage heart failure. Devices significantly affect patient physiology, leading to unique complications and different drug treatment strategies. The pharmacist is an integral part of a multidisciplinary team and has the responsibility to help patients use their medicines safely and appropriately. It is important to anticipate common postoperative complications and prepare appropriate treatments for them. This article reviews the current guidelines and research literature on the management of pharmacotherapy in patients with LVAD, integrates clinical research practice, summarizes the medication relevant experience and presents a review.

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC

Objective:To explore the application value of electromagnetic navigation technique in the removal of hematoma under neuroendoscope.Methods:Forty-three patients with supratentorial spontaneous cerebral hemorrhage, accepted removal of hematoma under neuroendoscope in our hospital from October 2015 to February 2019, were chosen in our study; 22 patients (navigation group) were performed the removal under the guide of real-time electromagnetic navigation, and 21 (non-navigation group) were performed the removal under neuroendoscope only. The amount of cerebral hemorrhage, operation time, residual amount of hematoma and hematoma clearance rate were compared between the two groups. Fugl-Meyer Assessment (FMA) was used to evaluate the motor function of the affected limbs two weeks after surgery. The anisotropy fraction (FA) values of fibers of affected pyramidal tracts and contralateral pyramidal tracts were examined by diffusion tensor imaging (DTI), and the relative FA (rFA) value (FA values of affected side/contralateral side) was calculated. Barthel index was used to evaluate the basic daily activities of the patients 6 months after surgery.Results:There was no significant difference between the navigation group and the non-navigation group in the amount of cerebral hemorrhage before surgery, amount of residual hematoma after surgery, hematoma clearance rate, and operation time ( P>0.05). FMA scores of upper and lower limbs, FA and rFA values of the affected side in the navigation group were significantly higher than those in the non-navigation group two weeks after surgery ( P<0.05). Barthel index of patients in the navigation group was statistically higher than that of the non-navigation group 6 months after surgery ( P<0.05). Conclusion:Electromagnetic navigation technique can guide endoscopy to effectively clear the supratentorial hypertensive cerebral hemorrhage without obviously increasing the operation time; effective protection of pyramidal fibers can improve the prognoses of patients.

Polylactic acid is synthesized indirectly by the polymerization method, according to the standard GB/T 16886.18-2011, the evaluation parameters and methods about chemical characterization of polylactic acid have been established. By using rigorous and comprehensive comparative analysis, the chemical equivalency of domestic and imported polylactic acid materials has been proved, along with the "Medical Device Biology Evaluation and Review Guide", paving the way of using domestic polylactic acid in implantable medical devices.
Equipment and Supplies ; Lactic Acid ; Polyesters ; chemistry ; Polymers

Objective To establish a pure planarian Dugesiaasexual strain in China.Methods The planarian worms were collected from a wild stream,and then made the worm grow after amputation in the lab.To establish an asexual strain through cutting and culturing for the single worms.Results After ten years and more than ten thousand experiments,an asexual pure planarian strain Dugesia ZB-1 originated from Shandong Zibo area was established.It grows stably under laboratory controlled conditions.Conclusions The establishment of DugesiaZB-1 Priovides a solid foundation for further experiments and promoting planarian research in our country and participation in the field of the international planarian research.

Objective To investigate the infection situation of intestinal nematodes and knowledge about the prevention and control of intestinal nematodiasis,so as to explore the effective control measures in Jingjiang City. Methods The towns where more floating people lived were randomly selected and the infection situation of intestinal nematodes was investigated with Kato-Katz method,and the residents'awareness of the prevention and control of nematodiasis was surveyed with questionnaires. Re-sults From 2013 to 2015,totally 4555 local residents and 2278 floating people were investigated in Jingjiang City. The infec-tion rate of intestinal nematodes was 0.29%(13 cases)in the local people,while the rate was 0.75%(17 cases)in the floating people,and the difference was significant(χ2=7.380,P<0.01). The differences of the intestinal nematode infection rates be-tween sexes in both local residents and floating people were not significant(χ2=0.010,0.048,both P>0.05). The awareness rate of intestinal nematodiasis prevention and control of the local residents was significantly higher than that of the floating peo-ple(χ2 =9.649-164.533,all P<0.01). Conclusion The floating people is the focus of intestinal nematodiasis control,and the health education of ancylostomiasis control should be strengthened in Jingjiang City.

Objective To understand the source of knowledge on schistosomiasis prevention and control and the acceptable degree on different propagation patterns of population in Jingjiang City after schistosomiasis transmission?interrupted,so as to provide the evidence for the production of suitable materials for health education. Methods The permanent residents,floating population as well as the primary school students in Grade 5 and 6 in riverside regions in Jingjiang City were selected as the in?vestigation objects,the information propagation condition and the knowledge source,and the expected propagation patterns were investigated by questionnaires. Results The popularizing rates on the television,computer and mobile phone of the villag?ers were 99.81%,84.16% and 87.78%,respectively. Both the two investigated schools had the independent TV network,broad?cast and multimedia,and all the computer classroom could connected to Internet. The main sources on schistosomiasis control of permanent residents and floating population were folders and the exhibition board(62.0% and 40.5% respectively),the substan?tial material(42.0% and 33.5% respectively)and TV(40.5% and 36.0% respectively),while those of the students were video CD(100%),substantial material(99.5%)and folders and the exhibition boards(84.2%). The propagation ways with high ac?ceptable degrees among the residents and floating population were substantial material,folders and the exhibition boards and short messages by mobile phone,while those among the students were video CD,substantial material,folders and the exhibition boards. Conclusion The material on health education should be targeted to the demands of the different populations and their condition of information propagation,in addition,the Internet material should be developed and the communicational channels should be broaden.