ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
Animals ; Alzheimer Disease/pathology* ; Pseudogenes/genetics* ; Mice ; Memory Disorders/metabolism* ; MicroRNAs/genetics* ; Disease Models, Animal ; Spatial Learning/physiology* ; Mice, Transgenic ; Presenilin-1/genetics* ; Male ; Amyloid Precursor Protein Secretases/metabolism* ; Mice, Inbred C57BL ; Aspartic Acid Endopeptidases/metabolism*

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Objective To evaluate and summarize the evidence related to targeted temperature management in brain injury patients with ICU for health care workers and decision makers.Methods We systematically searched from the guideline websites,domestic and foreign databases and association official websites to collect the literature including guidelines,expert consensuses,clinic decision-making,evidence summaries and systematic reviews,according to the 6s evidence model.The search time limit was from January 2012 to April,2023.Evidence was extracted after the quality evaluation of the literature was conducted by evidence-based researchers.Results A total of 19 articles were incorporated,including 6 guidelines,3 clinic decision-making,5 expert consensuses,4 systematic reviews and 1 evidence summary.Finally,25 pieces of best evidence were formed from 10 aspects,temperature range,starting time,body temperature monitoring,pipeline management,analgesia and sedation management,mechanical ventilation and oxygenation management,hemodynamic support,nutrition management,condition monitoring and prognosis evaluation.Conclusion The best evidence for management of targeted temperature in brain injury patients with ICU in this study is scientific and comprehensive,providing the evidence-based basis for medical staff to standardized management of targeted temperature in critically ill patients in clinical practice.

Objective:To explore the correlation between serum NLR and SII levels and postmenopausal osteoporotic vertebral compression fracture (OVCF) and to analyze the short-term prognostic value.Methods:A total of 132 patients with postmenopausal OVCF admitted to our hospital from Dec. 2018 to Dec. 2021 were selected as the study group, and 98 patients with postmenopausal osteoporosis but did not suffer from OVCF were selected as the control group. According to the recurrence of postmenopausal OVCF fractures, the ROC curves of NLR and SII were plotted, and their prognostic value for postmenopausal osteoporosis OVCF was analyzed.Results:NLR level was 2.96±0.41 and STI level was 39.41±23.45 in the control group. The level of NLR was 3.42±0.32 and SII was 431.77±31.14 in the research group ( P<0.05) . Multivariate Logistic regression analysis showed that lumbar bone density ( OR=0.030, 95%CI: 0.001-0.832, P=0.042) , NLR level ( OR=29.43, 95%CI: 9.840-103.6, P=0.001) and SII level ( OR=1.048, 95%CI: 1.034-1.066, P=0.001) were all risk factors affecting postmenopausal OVCF. NLR (3.77±0.22) and SII (441.32±29.68) in the recurrent fracture group were higher than NLR (3.27±0.22) and SII (426.87±30.57) in the non-recurrent fracture group, and the differences were statistically significant (all P<0.05) , multivariate Logistic regression analysis showed lumbar spine bone density ( OR=8.56×10 4, 95% CI: 3.884-2.992×10 10, P=0.045) , NLR level ( OR=1.243×10 -8, 95% CI: 2.911×10 -13-1.072×10 -5, P=0.001) and SII level ( OR=0.938, 95% CI: 0.885-0.976, P=0.008) were all influencing factors affecting the postoperative treatment effect of postmenopausal OVCF, and ROC results showed that both NLR (AUC=0.86, 95% CI: 0.77-0.94, P<0.001) and SII (AUC=0.76, 95% CI: 0.67-0.85, P<0.001) had good prognostic value for postmenopausal OVCF. Conclusion:NLR and SII are risk factors for OVCF in postmenopausal osteoporosis patients, and have good short-term prognostic value.

Objective:To explore the risk factors of unplanned readmission in patients with acute myocardial infarction, and to construct a risk prediction model.Methods:This study used cross-sectional survey method. A total of 270 acute myocardial infarction patients admitted from Tianjin Union Medical Cencer from March 2020 to March 2021 were evaluated in a cardiology department. We used the electronic medical record system to collect the patients′ data. Patients were divided into two groups according to the occurrence of readmission within 1 year or not. Logistic regression analysis was performed to identify risk factors and formulated prediction model.Results:Totally 81 patients (30%) were readmitted. Binary Logistic regression model showed that the independent influencing factors of unplanned readmission in acute myocardial infarction patients included smoking ( X1), hypertension ( X2), marital status ( X3), hospitalization days ( X4), percutaneous coronary intervention ( X5), and heart failure ( X6). Area under ROC curve was 0.840, the maximum value of the Youden index was 0.560, and the sensitivity was 85.2%, the specificity was 70.8%, and the cutoff value was 0.377. Prediction model expression of unplanned readmission risk in patients with acute myocardial infarction was Logit(p/1-p)=-4.012+1.172 X1+1.104 X2+0.992 X3+0.118 X4+1.191 X5+1.093 X6. Conclusions:The risk prediction model of unplanned readmission in patients with acute myocardial infarction established in this article was with a good predictive effect, and it could be used in early identification of those patients with high-risk in unplanned readmission. At the same time, combined with the risk factors of depression, targeted intervention measures can be formulated.

OBJECTIVE To explore the difference in th e mechanis m of baicalein and wogonin inhibiting the energy metabolism of hepatoma cells. METHODS Human hepatoma HepG 2 cells were divided into blank control group （without medicine），different dose groups of baicalein and wogonin （1.25，2.5，5，10 and 20 μmol/L）. The effects of baicalein and wogonin on the viability of HepG 2 cells were detected by MTT assay. HepG 2 cells were divided into blank control group （without medicine），baicalein group and wogonin group. After administration ，the concentration of ATP in cell was detected by enhanced ATP kit. The levels of cell glycolysis and mitochondrial energy metabolism were evaluated by glycolysis and mitochondrial pressure test kit ；the affinity of baicalein and wogonin with key enzymes of energy metabolism was predicted by molecular docking ，and the key enzymes of energy metabolism with high affinity were screened ；the expression of key enzymes of energy metabolism was detected by Western blot. RESULTS Within the dose range of 2.5-20 μmol/L，the half inhibitory concentrations of baicalein and wogonin were 12.84 and 24.09 μmol/L；baicalein 1.25 μmol/L and wogonin 2.5 μmol/L had no effect on cell viability ，so it was selected as the dosage for subsequent experiments. Compared with blank control group ，the concentration of ATP in HepG 2 cells decreased significantly in baicalein group and wogonin group （P＜0.05）；the inhibitory effects on basic acidification rate of HepG 2 cells in wogonin group were significantly stronger than those of baicalein group （P＜0.05），but there was no significant difference between them on the basic oxygen consumption rate （P＞0.05）；baicalein had strong binding to pyruvate kinase M 2 and mitochondrial enzyme complexes Ⅰ（CⅠ），C Ⅱ and C Ⅳ，while wogonin only had strong binding to pyruvate kinase M 2； wogonin could significantly down-regulate the protein expressions of hexokinase ，phosphofructokinase，pyruvate kinase M 2，CⅠ， C Ⅱ and C Ⅳ（P＜0.05），but there was no statistical significance in the effect of baicalein on the regulation of these enzymes （P＞ 0.05）. CONCLUSIONS Both baicalein and wogonin can inhibit the energy metabolism of hepatoma HepG 2 cells，but the mechanism is different ：the effect of baicalein is related to the activity of key enzymes ，while the effect of wogonin is related to the inhibition of the expression of key enzymes of energy metabolism.