ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Objective To investigate the effects of Aconite decoction （AD） on the viability and polarization of murine RAW264.7 macrophages induced by lipopolysaccharide （LPS） or interleukin-4 （IL-4）. Methods Cytotoxicity of AD was assessed by the CCK-8 assay. RAW264.7 cells were polarized toward M1 phenotype by LPS or M2 phenotype by IL-4, followed by treatment with varying concentrations of AD. Macrophage polarization was analyzed by flow cytometry. Quantitative PCR was performed to measure mRNA expression of polarization-associated markers （IL-6, iNOS, Arg1, and Ym1）. ELISA was used to quantify secreted cytokines （TNF-α and IL-10）in the supernatant. Results At non-toxic concentrations, IL-6 and iNOS mRNA levels in LPS-stimulated cells were significantly upregulated while Arg1 and Ym1 expression in IL-4-treated groups were downregulated by AD. Concurrently, TNF-α secretion in LPS-induced M1 polarization was enhanced but IL-10 production in IL-4-induced M2 polarization was suppressed by AD. Conclusion AD could promote macrophage proliferation and viability, augments LPS-driven M1 polarization, and inhibit IL-4-mediated M2 polarization, which provided experimental evidence for the potential application of AD in tumor immunotherapy.

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Thirteen novel diterpenoids, comprising seven tiglianes (walliglianes G-M, 1-7), four rhamnofolanes (wallinofolanes A-D, 8-11), and two daphnanes (wallaphnanes A and B, 12 and 13), together with two known rhamnofolane diterpenoids (euphorwallside H and euphorwallside I, 14 and 15), were isolated and characterized from Euphorbia wallichii(E. wallichii). The chemical structures of these compounds were elucidated through nuclear magnetic resonance (NMR), mass spectrometry (MS), and quantum chemical calculations. Compounds 9 and 11 demonstrated protective effects against H₂O₂-induced BV-2 microglial cell damage. Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR, GSTP1, and SHBG.
Euphorbia/chemistry* ; Antioxidants/isolation & purification* ; Diterpenes/isolation & purification* ; Molecular Structure ; Mice ; Molecular Docking Simulation ; Animals ; Hydrogen Peroxide/toxicity* ; Cell Line ; Microglia/drug effects*

Objective:To understand the learning interest of college students majoring in Bioinformatics in Shenyang Medical College and its influencing factors,so as to provide a strong basis for future teaching reform and curriculum setting.Method:After the actual teaching,a self-made questionnaire was used to conduct a quantitative survey on the first-year students majoring in Bioinformatics of Shenyang Medical College to understand their learning interest and analyze its influencing factors.Results:The questionnaire survey found that students majoring in Bioinformatics had different interest points for all 9 courses,different teaching links and different teaching methods in the second semester of freshman.Students had a general high interest in Introduction to Bioinformatics and Introduction to Biometrics.In the Introduction to Bioinformatics course,students were more interested in the history of bioinformatics,but less interested in algorithm-related knowledge points.In the Introduction to Biometrics course,students were more interested in the application cases of biometric recognition,but less interested in laws and regulations of biometrics.The interest of students in learning mainly lied in whether it is conducive to the postgraduate entrance examination.Conclusion:Through strengthen the education of bioinformatics related courses,enhance students'understanding of bioinformatics knowledge and improve their interest in Bioinformatics by analyzing the results of students'questionnaire.

This paper reviews the requirements for the budget management systems for public hospitals established by the Ministry of Finance and the National Health Commission.It analyzes the difficulties and problems existing in the establishment of budget projects,budget formulation,and the connection between budget analysis and performance assessment.Combined the case of the hospital's comprehensive budget management system construction concerning the establishment and inclusion of information projects,the paper proposes the feasibility of constructing a budget project library management system to effectively address the is-sues.This approach aims to gradually achieve the goal of improving project fine management and perfecting the dual parallel of project life cycle budget execution and performance management.

Huangqin Decoction is a classic formula published in the Catalogue of Ancient Classical Famous Prescriptions(the Sec-ond Batch).This paper systematically collates,researches and analyzes the ancient and modern clinical literature that records Huan-gqin Decoction,sorts out key issues such as the prescription origin,composition,medicine origin,processing method,usage and dos-age,efficacy and indications of Huangqin Decoction,and performs predictive analysis on its quality markers(Q-Marker)to provide lit-erature and theoretical support for the clinical application and preparation development of Huangqin Decoction from the entire process of textual research-preparation development-quality evaluation.After analysis and research,it is found that Huangqin Decoction is de-rived from Zhang Zhongjing's Treatise on Cold Damage.It consists of Scutellaria baicalensis,Radix Paeoniae Alba,and Glycyrrhiza,with Jujube serving as the guiding herb.The medicine origin follows the 2020 edition of the Chinese Pharmacopoeia.Scutellaria ba-icalensis and Radix Paeoniae Alba are taken in the raw form;Glycyrrhiza is lightly fried and Jujubes with sliced pieces.The doasge of medicine is 11.19 of Scutellaria baicalensis,7.46 g of Radix Paeoniae Alba and Glycyrrhiza,and jujubes are added or subtracted ac-cording to the situation.The method of preparation and administration is that all herbs are added with 2 000 mL of water,decocting to 600 mL.The decoction can be consumed warm 3 times a day at any suitable time.The formula was commonly used in ancient times for dysentery,but now it is also used for other digestive system diseases such as ulcerative colitis and chronic colitis,which are mainly characterized by diarrhea.The suggested Q-markers for Huangqin Decoction are baicalin,baicalein,wogonin,paeoniflorin,glycyrrhi-zin and glycyrrhizic acid.

BACKGROUND:There is an increasing demand for orthodontic treatment,and periodontally accelerated osteogenic orthodontics(PAOO)technique can make it possible to move orthodontic teeth that are limited by thin alveolar bone. OBJECTIVE:To investigate the biomechanics of orthodontic tooth movement before and after periodontally accelerated osteogenic orthodontics(PAOO)surgery to increase alveolar bone volume using the three-dimensional finite element method. METHODS:A patient undergoing PAOO surgery before orthodontic treatment to increase bone volume on the labial side of the mandibular anterior region was selected.The patient was under invisible orthodontics.Two three-dimensional finite element models were constructed based on the patient's preoperative and 6-month postoperative cone beam CT data.Both models simulated the movement of tooth 33:experiment Ⅰ:distal-central movement of 0.25 mm;experiment Ⅱ:lingual movement of 0.25 mm;and experiment Ⅲ:intrusion movement of 0.10 mm.The stress distribution and initial displacement trend of tooth 33,periodontal ligament and surrounding alveolar bone under the action of the invisible aligner were analyzed before and after the PAOO procedure. RESULTS AND CONCLUSION:Dental stress analysis:In the same orthodontic tooth movement,the maximum Von-Mises stress and overall stress values of tooth 33 were all higher before surgery than after surgery;there were similar distribution areas of maximum equivalent stress and overall distribution trends of Von-Mises stress before and after surgery.Periodontal ligament stress analysis:In the same orthodontic tooth movement,the maximum Von-Mises stress and overall stress values of the periodontal ligament were higher before surgery than after surgery,and there were similar distribution areas of the maximum equivalent stress and overall distribution trends of Von-Mises stress before and after surgery.Alveolar bone stress analysis:In the same orthodontic tooth movement,the maximum Von-Mises stress values of the alveolar bone around tooth 33 were higher before surgery than after surgery,while the equivalent stress distribution showed a gradual decrease from the top of the alveolar ridge to the root.Initial displacement analysis:In the same orthodontic tooth movement,the initial displacements in the main displacement direction for all six observation points of tooth 33 were smaller before surgery than after surgery,and showed a tendency to gradually decrease from the tooth tip to the apex.Therefore,there were differences in the biomechanical characteristics of orthodontic tooth movement before and after the PAOO surgery.With the clear aligner,the postoperative equivalent stress values on the dentition,periodontal ligament,and surrounding alveolar bone were lower than before the surgery,and the initial displacements of the orthodontic teeth after the surgery are larger than before.These findings suggest that PAOO can release the restriction of thin alveolar bone on the movement of orthodontic tooth by increasing alveolar bone thickness,effectively improving the force on the roots,periodontal ligament,and alveolar bone,avoiding the stress concentration on orthodontic tooth in the thin alveolar bone area that can cause complications when moving,and improving the efficiency of tooth movement.