Objective:To explore the hypothesis of "pathogen storage pool" by analyzing the local microbial community of adenoids. Methods:Under the guidance of a 70° nasal endoscope, sterile swabs were used to collect secretions from the adenoid crypts of the subjects. The samples were sent to the laboratory for DNA extraction and standard bacterial 16S full-length sequencing analysis. Results:At the species level, the top three microbial communities in adenoid crypts were Bacillus subtilis（18.78%）, Fusobacterium pyogenes（11.42%）, and Streptococcus pneumoniae（9.38%）. Conclusion:The local microbial community of adenoids exhibits a high degree of diversity, including microbial communities from the oral cavity and gastrointestinal tract. Our research results support the hypothesis that adenoids act as a " pathogen reservoir".
Humans ; Adenoids/microbiology* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Streptococcus pneumoniae/isolation & purification* ; Bacillus subtilis/genetics* ; DNA, Bacterial/analysis*

Objective:To explore the current dietary patterns and influencing factors of patients with coronary heart disease (CHD) in severe cold regions, aiming to provide scientific evidence for developing targeted dietary interventions.Methods:A total of 340 patients with CHD who visited the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between September and December 2023 were selected using convenience sampling. Patients were assessed using a general information questionnaire, Semi-Quantitative Food Frequency Questionnaire, Food Choice Questionnaire, Nutritional Knowledge Questionnaire, 7-Item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9.Results:A total of 340 questionnaires were distributed, and 333 valid questionnaires were collected, with an effective response rate of 97.94% (333/340). Two dietary patterns were identified among patients with CHD in severe cold regions: a "fruit-nut-dairy" dietary pattern and a "meat-seafood-grain" dietary pattern. Factors influencing the "fruit-nut-dairy" dietary pattern included gender, nutritional knowledge, and food choice motivations such as accessibility, sensory appeal, brand and packaging, and emotional dimensions ( P<0.05). Factors influencing the "meat-seafood-grain" dietary pattern included body mass index (BMI), living alone or not, monthly income, and food choice motivations such as convenience, health attributes, sensory appeal, and price ( P<0.05) . Conclusions:When providing dietary interventions for CHD patients, targeted control of factors such as gender, BMI, living alone or not, monthly income, nutritional knowledge, and key elements of food choice motivations may optimize patients' irrational dietary structures and reduce adverse disease outcomes.

Objective:To explore the current dietary patterns and influencing factors of patients with coronary heart disease (CHD) in severe cold regions, aiming to provide scientific evidence for developing targeted dietary interventions.Methods:A total of 340 patients with CHD who visited the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between September and December 2023 were selected using convenience sampling. Patients were assessed using a general information questionnaire, Semi-Quantitative Food Frequency Questionnaire, Food Choice Questionnaire, Nutritional Knowledge Questionnaire, 7-Item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9.Results:A total of 340 questionnaires were distributed, and 333 valid questionnaires were collected, with an effective response rate of 97.94% (333/340). Two dietary patterns were identified among patients with CHD in severe cold regions: a "fruit-nut-dairy" dietary pattern and a "meat-seafood-grain" dietary pattern. Factors influencing the "fruit-nut-dairy" dietary pattern included gender, nutritional knowledge, and food choice motivations such as accessibility, sensory appeal, brand and packaging, and emotional dimensions ( P<0.05). Factors influencing the "meat-seafood-grain" dietary pattern included body mass index (BMI), living alone or not, monthly income, and food choice motivations such as convenience, health attributes, sensory appeal, and price ( P<0.05) . Conclusions:When providing dietary interventions for CHD patients, targeted control of factors such as gender, BMI, living alone or not, monthly income, nutritional knowledge, and key elements of food choice motivations may optimize patients' irrational dietary structures and reduce adverse disease outcomes.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.

The call of the times to"promote education informatization towards a new journey"has posed new challenges to edu-cation,and the education industry should be committed to modernizing education through education informatization.In recent years,online teaching has become the norm.In this context,our teaching team introduced short video teaching into teaching innovation to spread Animal Immunology knowledge.Animation and ideological and political elements were integrated into each video,making knowledge points from"abstract"to"concrete",which stimulated students'interest in learning and cultivate the quality of rigorous scholarship and moral cultivation.The short video comment area has become a medium for interaction between teachers and students.The real-time feedback of the data platform provides a reference for the optimization and design of teaching content.The short video teaching practice effectively solves the"pain points"in traditional teaching and makes the obscure animal immunology knowledge more understandable.Students have increased their interest in learning,using fragmented time to actively acquire knowledge,achieving the effect of improving the teaching quality of animal immunology through online teaching resources.

OBJECTIVE To heterologously express and purify bioscavenger organophosphorus hydrolase(OPH),and evaluate its ability to resist ethyl paraoxon poisoning in vivo.METHODS The Escherichia coli expression strain of OPH was constructed and purified by Ni-column affinity chroma-tography and gel filtration chromatography,and the purified product was identified by mass spectrometry.The enzyme activity and kinetic constants(Km,Vmax,kcat and kcat/Km)were measured using ethyl paraoxon as the substrate.Twelve SD rats were randomly divided into the experimental group and control group.The experimental group was given 1 mg·kg-1 of OPH solution by iv administration while the control group was given the same volume of normal saline.After administration,the two groups were immedi-ately sc administration with 2×LD50 ethyl paraoxon(0.86 mg·kg-1).The state of the rats was observed and the poisoning symptoms were scored.The survival rats were given 2×LD50 ethyl paraoxon every 24 h,and the survival curve and symptom score chart were drawn according to survival and poisoning symp-toms of the rats to evaluate the anti-organophosphorus poisoning ability of OPH.RESULTS The expres-sion strain of OPH in E.coli was successfully constructed.After two-step purification,a single band of OPH was obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis,indicating that OPH had high purity,and the prepared protein sequence was consistent with the target protein.For OPH,Km=7.5×10-5 mol·L-1,Vmax=2.2×10-7 mol·L-1·s-1,kcat=158.4 s-1,kcat/Km=2.1×106 L·mol-1·s-1.The rats in the control group showed obvious poisoning symptoms after being given 2×LD50 ethyl paraoxon,and all rats died with in 15 min.The rats in the experimental group did not show poisoning symptoms after the first exposure,and the poisoning symptoms gradually deepened after continuous exposure until all the rats died on the 4th day.CONCLUSION OPH with high purity is successfully prepared in this study,and OPH could effectively resist ethyl paraoxon poisoning in rats.

Objective:To evaluate the effect of patient-controlled intravenous analgesia (PCIA) with esketamine mixed with hydromorphone on the postoperative sleep quality in pediatric patients.Methods:This was a prospective randomised controlled study. One hundred pediatric patients of both sexes, aged 4-12 yr, with a body mass index of 13-26 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective abdominal surgery with general anesthesia, who agreed to use postoperative patient-controlled intravenous analgesia in our hospital from January to November 2023, were divided into esktamine mixed with hydromorphone group (EH group) and hydromorphone group (H group), with 50 patients in each group. PCIA solution contained esketamine 1 mg/kg and hydromorphon 0.1 mg/kg in 100 ml of 0.9% sodium chloride in EH group and hydromorphone 0.2 mg/kg in 100 ml of 0.9% sodium chloride in H group. The Pittsburgh Sleep Quality Index was used to evaluate the preoperative sleep quality by asking pediatric patients themselves or their guardians. On the morning of 1-3 days after surgery, the numeric rating scale (NRS) was used to evaluate the sleep quality of the first 3 nights after surgery. At 24 and 48 h after surgery, the FLACC pain scale was used to evaluate the intensity of pain. The consumption of hydromorphone within 48 h after surgery and the incidence of postoperative adverse reactions such as nausea, vomiting, itching and delirium were recorded. Results:Compared with group H, the NRS score was significantly increased on the 1st postoperative night, the ratio of poor sleep quality was decreased ( P<0.05), and no significant change was found in the NRS score on the 2nd or 3rd postoperative night and ratio of poor sleep quality ( P>0.05), and the FLACC pain scale score at 24 and 48 h after surgery and consumption of hydromorphone within 48 h after surgery were decreased in group EH ( P<0.05). There was no significant difference in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:PCIA with esketamine mixed with hydromorphone can improve the postoperative sleep quality in pediatric patients.

Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.