The red doctor culture runs through the development process of China’s red health undertakings. It is a unity of revolutionary culture， health culture， and educational culture， providing rich educational resources for ideological and political education in medical colleges and universities. From the perspective of historical logic， red doctor culture is rooted in the traditional medical ethics thought of “medicine is the art of benevolence” in ancient China， as well as has evolved alongside the century-long development of the health and well-being undertakings led by the Communist Party of China. From the perspective of theoretical logic， red doctor culture is closely related to Xi Jinping Thought on Culture， the principle of the dialectical relationship between social existence and social consciousness， and the theory of cultural leadership. From the perspective of practical logic， it is necessary to clarify the practical path from three aspects， namely accurately grasping the Marxist theoretical foundation of the red doctor culture and highlighting its orientation of the ideological and political education of medical students； making effective use of existing resources of red doctor culture to improve the content of ideological and political education and consolidate the foundation of red doctor literacy； optimizing the construction of teaching teams for ideological and political theory courses in medical colleges and universities. From the perspective of value orientation， the red doctor culture is conducive to cultivating the professional ethics spirit of medical students， meeting the teaching needs of ideological and political theory courses in medical colleges and universities， and assisting the construction of the healthy China initiative.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

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

BACKGROUND:Most of the silver coating materials prepared using active screen plasma technology in the past do not involve the nanotechnology field.The formed silver coating is in a"thin film"form,which is coated on the surface of the substrate,and the distribution of silver particles on the surface is uneven.Its long-term antibacterial ability is challenged. OBJECTIVE:To prepare nano silver coatings capable of being"buried"within stainless steel(SS)substrates using active screen plasma surface modification(ASPSM)and to observe antibacterial activity. METHODS:The nano-silver coating was prepared by ASPSM technique on stainless steel substrate.Three groups of coating samples were prepared by adjusting the bombardment time(1,2,and 4 hours),which were denoted as 1 h-Ag-ASPSM@SS,2 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,respectively.The antibacterial activity of the coatings was analyzed by antibacterial ring test and Gram staining.The antibiotic coating samples of gentamicin combined with vancomycin were prepared by using stainless steel as substrate and were recorded as ACNs.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were inserted into Staphylococcus aureus or Pseudomonas aeruginosa suspension,respectively.The long-acting(84 days)antibacterial activity of the samples was analyzed by coating plate method.Bone marrow mesenchymal stem cells were co-cultured with stainless steel,2 h-Ag-ASPSM@SS,and ACNs,respectively.CCK-8 assay,dead/alive staining,and lactate dehydrogenase activity of cell supernatant were detected.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were taken after continuous exposure to Staphylococcus aureus suspension for 12 weeks.The amount of residual viable bacteria on the surface of the material was evaluated by spread plate method.Vancomycin drug sensitive disk method was used to evaluate the resistance of residual live bacteria on the surface of materials. RESULTS AND CONCLUSION:(1)With increasing bombardment time,the diameter of nano silver on the sample surface and the silver content in the coating gradually increased.Among them,the 2 h-Ag-ASPSM@SS exhibited the highest surface silver content while forming uniformly spherical nanoparticles.(2)Antibacterial ring test and Gram staining results demonstrated that compared with 1 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,the 2 h-Ag-ASPSM@SS exhibited better inhibitory effect on Staphylococcus aureus and pseudomonas aeruginosa.After co-culturing with bacteria for 42 and 84 days,the number of viable bacteria on the spread plate method was significantly lower in the 2 h-Ag-ASPSM@SS group compared to the stainless steel and ACNs groups.After co-culturing with Staphylococcus aureus for 84 days and Pseudomonas aeruginosa for 42 days,the number of viable bacteria on the surface of the eluate from the ACNs group was higher than that of the stainless steel group.(3)CCK-8 assay,live/dead staining and lactate dehydrogenase activity of cell supernatant displayed that 2 h-Ag-ASPSM@SS did not have obvious cytotoxicity.ACNs showed obvious cytotoxicity.(4)After co-culture with Staphylococcus aureus for 12 weeks,the residual viable bacteria on the surface of 2 h-Ag-ASPSM@SS group was less than that of stainless steel group,and the residual viable bacteria on the surface of the ACNs group was more than that of stainless steel group.Compared with the stainless steel group,the sensitivity to vancomycin was significantly decreased in the ACNs group(P＜0.001),and there was no significant change in sensitivity to vancomycin in 2 h-Ag-ASPSM@SS group(P＞0.05).(5)The above results indicate that the silver nanoparticle coated stainless steel greatly improves the deposition efficiency of silver nanoparticles on the stainless steel surface and has long-lasting antibacterial properties and good cell compatibility.

Objective:To explore the application of medical dialectics combined with problem-oriented teaching based on textbooks in hematology internship teaching.Methods:A total of 100 undergraduate students who practiced in the Department of Hematology of the First Hospital of Jilin University from 2022 to 2023 were selected as the research subjects. Students were randomly assigned to a control group and an observation group, with 50 students in each group. The control group received traditional teaching, while the observation group received medical dialectics combined with textbook-based problem-oriented teaching. We assessed the theoretical and operational scores, classroom performance, comprehensive abilities, and teaching satisfaction of two groups of students using t-test and χ 2 test in SPSS 22.0. Results:The theoretical and operational scores of the observation group were (94.26±5.35) points and (92.68±4.72) points, respectively. The theoretical and operational scores of the control group were (86.16±5.42) points and (81.52±5.28) points, respectively. The differences between the two groups were statistically significant ( P<0.001). The recognition rates were significantly higher by students in the observation group than in the control group ( P<0.05) in terms of improving learning efficiency, self-learning ability, understanding and comprehensive analysis of diseases, problem-solving ability, language and organizational expression ability, integration of theory and practice, clinical thinking ability, and independent thinking ability. The satisfaction with teaching was higher in the observation group than in the control group ( P<0.05) in terms of teaching attitudes, teaching methods, teaching arrangements, practicality of teaching content, clear explanation of teaching theories, and outstanding teaching objectives. Conclusions:The medical dialectics combined with textbook-based problem-oriented teaching can improve the assessment scores of medical students, while helping to cultivate their comprehensive abilities and develop good clinical diagnosis and treatment thinking.

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.

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.

[Objective] To evaluate the efficacy and safety of zero-pressure percutaneous nephrolithotomy (PCNL) combined with hands-free pneumatic lithotripsy in the one-stage treatment of calculous pyonephrosis in the non-acute infection phase. [Methods] Clinical data of 15 patients' treated during Feb.2022 and Dec.2023 were retrospectively analyzed.Double-sheath negative pressure PCNL was adopted, with zero-pressure gravity perfusion where the perfusion height was at the level of the patients' kidney, not exceeding 20 cm above the kidney.Pneumatic lithotripsy was performed without the need to hold the device with hand. [Results] The median stone diameter was 28 (range 22—40) mm, with a median stone density of 1028 (range 765—1305) Hu.All operations were successful.The median operation time was 55 (range 35—90) min.Postoperative low fever (Clavien grade Ⅰ) occurred in 1 case, and high fever (Clavien grade Ⅱ) occurred in 1 case, with no complications of Clavien grade Ⅲ or above.The initial stone-free rate was 73.3%, and the stone-free rate after one month was 93.3%. [Conclusion] For patients with calculous pyonephrosis in the non-acute infection phase, one-stage treatment using zero-pressure PCNL combined with hands-free pneumatic lithotripsy demonstrates good efficacy and safety.

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 examine the compliance of and factors affecting target attainment of serum trough concentration of norvancomycin in ICU patients,and the effects of different trough concentrations on clinical efficacy and renal impairment.Methods Adult patients admitted to the Department of Critical Care Medicine of Huangshan People's Hospital and receiving intravenous infusion of norvancomycin from January 2020 to December 2022 were included.The dosing regimens and steady-state trough concentrations of norvancomycin were analyzed.The clinical efficacy and renal impairment were compared between different trough concentration levels.The compliance of trough concentration in critically ill patients with different renal functions was examined.Logistic regression analysis was performed to profile the factors possibly affecting the trough concentration of norvancomycin.Results A total of 97 patients were included.The target serum trough concentration(10-20 mg/L)was reached in only 33.0％(32/97)of the critically ill patients.The serum trough concentration was below the target in 51.5％(50/97)of the patients,above the target in 15.5％of the patients.The clinical cure rate and incidence of renal impairment were significantly different among the three groups of patients with different trough concentrations(P＜0.05).The compliance with target serum trough concentration varied with different renal function tests(P＜0.05).Augmented renal clearance and normal renal function were associated with trough concentrations lower than the target.As renal dysfunction got worse,serum trough concentration was more probably higher than the target(P＜0.05).Univariate analysis showed that daily dose,age,gender,height,weight,body mass index(BMI),APACHE Ⅱ score,sequential organ failure assessment(SOFA)score,blood creatinine,urea nitrogen,procalcitonin,concomitant septic shock,and use of norepinephrine were significantly correlated with trough concentrations of norvancomycin(P＜0.05).Multivariate logistic regression analysis indicated that age,SOFA score,blood urea nitrogen,gender,and norepinephrine use were independent factors affecting the serum trough concentration of norvancomycin(P＜0.05).Conclusions The serum trough concentration of norvancomycin varied with renal function states in ICU patients.It is difficult to achieve the steady-state target trough concentration(10-20 mg/L).The clinical cure rate is lower when the trough concentration is lower than the target.As the trough concentration increases,the incidence of renal impairment increases.Age,SOFA score,urea nitrogen,gender,and norepinephrine use are independent factors affecting the serum trough concentrations of norvancomycin.