BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Subarachnoid Hemorrhage/complications* ; Inflammasomes/metabolism* ; Rats ; Mice ; Neuroinflammatory Diseases/metabolism* ; WNK Lysine-Deficient Protein Kinase 1/genetics* ; Male ; Humans ; Chlorides/metabolism* ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; Brain Injuries/metabolism* ; Microglia/metabolism* ; Protein Serine-Threonine Kinases

Objective: To evaluate the effectiveness of health belief model-based health education intervention in improving blood pressure control of patients with hypertension in community settings. Methods: From September 2016 to September 2017, 400 newly diagnosed patients with hypertension were recruited from 6 community healthcare centers with comparable population size and health services in the Shunyi District of Beijing. All community healthcare centers were randomly assigned to the intervention group (206 patients) and the control group (194 patients). Patients in the intervention group received 3 lectures (20-30 min for each) of health belief model-based health education. Patients in the control group received usual care. The basic characteristics, health beliefs, and health literacy were collected, and blood pressure was measured before and after the intervention, respectively. The difference-in-difference model was used to analyze the change of blood pressure and the influencing factors between two groups before and after the intervention. Results: A total of 134 patients in the intervention group and 129 patients in the control group completed the study. After adjusting for the age, gender, family income, medical insurance, chronic diseases and family history, the score of perceived barriers was increased by 1.65 (P=0.016), and perceived seriousness was decreased by 0.73 (P=0.018). The systolic blood pressure of patients was decreased by 7.37 mmHg (1 mmHg=0.133 kPa, P=0.001) and diastolic blood pressure was decreased by 4.07 mmHg (P=0.014), respectively. The β (95%CI) values were -7.37 (-11.88,-2.86) and -4.07 (-7.30, -0.84). The perceived susceptibility and self-efficacy had a significant influence on the blood pressure of patients (P<0.05). Conclusion Health belief model-based health education intervention could significantly improve the blood pressure control of patients with hypertension in the community settings.

Objective Explore the change of IL-1β and IL-18 expression in pulmonary hypertension induced by monocrotaline.Methods Divide the mouses into two groups, control group and experimental group (n=10).Establish rats pulmonary hypertension model induced by monocrotaline.Detect the model by ultrasound, myocardial cells HE dyeing and tunnel test;ELISA was used to detect the serum biological markers NF-κB, COX2, IL-6, IL-1β, TNF-α and NO;Immunohistochemical was used to detect the expression level of IL-1β and IL-18 in the lung tissue;the protein change of NLRP3 in the lung tissue was detected by Western blot.Results Serum biological markers of NF-κB, COX2, IL-6, IL-1β, TNF-α and NO are significantly increased in PAH rats(P<0.05);The expression of IL-1β, IL-18 in the lung tissue increased obviously(P<0.05);The NLRP3 protein expression was significantly higher in experimental group.Conclusions Changes of NLRP3 effect increase expression of IL-1β and IL-18and which may play an important role in pulmonary hypertension induced by monocrotaline.

Objective To discuss the clinical features of pregnant women with hypertrophic cardiomyopathy (HCM).Methods There were 28 patients with HCM who delivered in Renji hospital of Shanghai Jiaotong University from January 2000 to August 2012.Clinical data were analyzed,including diagnosis,cardiac functional grading,gestational weeks of delivery,delivery mode,birth weight,Apgar scores,etc.Results (1) Of all the 28 patients,14 (50％) were diaguosed before pregnancy and others (50％) were diagnosed during pregnancy.(2) Four cases were obstructive HCM (14％),3 with cardiac function grade Ⅰ and 1 with grade Ⅱ.Twenty four cases were non-obstructive HCM (86％),14 with cardiac function grade Ⅰ,9 with grade Ⅱ and 1 with grade Ⅳ.(3) Of all the 28 patients,4 had family history,18 (64％) had clinical symptoms or signs which occurred in 8-32 gestational weeks.Twenty-three cases had abnormal ECG (82％).Among them 21 had non-obstructive HCM (88％),with average interventricular septal thickness of(22 ± 3) mm.The other 2 patients had obstructive HCM,with average interventricular septal thickness of (23 ± 4) mm.7 patients (7/28,25 ％) had mild-to-moderate pulmonary hypertension [6 with non-obstructive HCM (6/24,25％)],and 10 patients had abnormal myocardial enzyme spectrum or troponin levels [9 with non-obstructive HCM (9/24,38％)].(4) Among all the patients,only one had vaginal delivery and others received cesarean section.Twenty-two patients had term pregnancies and 6 had preterm birth.The average gestational weeks of delivery in non-obstructive HCM and obstructive HCM were (36.5 ± 2.5) and (38.5 ± 0.4) weeks,respectively.The average birth weight of neonates were (2684 ± 563) and (3164 ± 321) g,and Apgar scores were 9.9 and 10 (10 minutes) respectively.Patients transferred to NICU after delivery were 8 and 0.There was 1 maternal death(with nonobstructive HCM whose ejection fraction was only 26％) and no perinatal death.Conclusions More attention should be paid to the clinical signs and abnormal ECG.HCM could be definitely diagnosed by timely echocardiography.Patients with hypertrophic cardiomyopathy were mainly non-obstructive HCM,with cardiac function grade Ⅰ and Ⅱ.Monitoring the change of ejection fraction during pregnancy would help.Perinatal outcomes were fine.

Objective This study analyzes the main technical fields and their mutual correlation concerning the international patents of acupuncture to provide decision support for the strategy of developing acupuncture related products.Methods Derwent Innovation Index was applied as the data source,Thomson Data Analyzer was adopted as the main analyzing tool,and the co-occurring clustering spectrum analysis method of international patent number (IPC) was used.Results Based on the retrieval and analyzed results,the main classification of international patent of acupuncture and the technical association diagram of Chinese medicine acupuncture patents were formed.Conclusion The main technical fields of acupuncture international patent included acupuncture needles,acupuncture instruments combined with drug and acupuncture instruments combined with modem physical methods as well as the point health care products.Among them,the methods applied in acupuncture,namely the magnetic therapy method,laser therapy,thermal therapy,roller and ball massage adopted in acupuncture point massage instruments which combine traditional herbal medicine,have already been the research hotspot of current acupuncture patent products.