ObjectiveTo investigate the immunomodulatory effect of polysaccharides from Astragali Radix-Angelicae Sinensis Radix herb pair（Qi-gui polysaccharides） on lipopolysaccharide（LPS）-induced RAW264.7 macrophages and to characterize the structure of the active component Qi-gui homogeneous polysaccharide（AAPS-4a）， and evaluate its protective effect on ulcerative colitis（UC）. MethodsThe effects of six Qi-gui polysaccharides（0.01-100 mg·L^-1） on the proliferation of RAW264.7 cells were assessed by cell proliferation and activity assay（CCK-8）， and enzyme-linked immunosorbent assay（ELISA） was used to investigate the effects of the six polysaccharides（3， 10 mg·L^-1） on the secretion levels of tumor necrosis factor（TNF）-α， interferon（IFN）-β， and nitric oxide（NO） in LPS-induced RAW264.7 cells. After screening for active polysaccharides， high-performance size-exclusion chromatography（HPSEC） was used to determine its homogeneity and relative molecular weight， then its characteristic functional groups were identified by Fourier transform infrared spectroscopy（FT-IR）， monosaccharide composition was analyzed by high performance liquid chromatography（HPLC）， methylation analysis combined with gas chromatography-mass spectrometry（GC-MS） was performed to determine the types and linkage modes of sugar residues， and one- and two-dimensional nuclear magnetic resonance（NMR） were used to identify the sugar residue composition and configuration of the active polysaccharide. Finally， experimental animals were divided into the normal group， model group， AAPS-4a low-dose group（50 mg·kg^-1）， AAPS-4a high-dose group（100 mg·kg^-1）， and sulfasalazine（SASP） group （75 mg·kg^-1）. Except for the normal group， the acute UC mouse model was induced using 3.5% dextran sulfate sodium salt（DSS）. Each treatment group was administered the corresponding dose via oral gavage for 7 days， and changes in body weight were recorded. After treatment， the spleen index and disease activity index（DAI） score were calculated， TNF-α and interleukin-6（IL-6） levels in the serum were detected by ELISA， and histopathological changes in colon tissue were observed by hematoxylin-eosin（HE） staining. ResultsAt the cellular level， AAPS-4a exhibited a dose-dependent inhibition of LPS-induced increases in TNF-α， IFN-β， and NO levels（P<0.01）. Structural characterization of AAPS-4a revealed that it was a homogeneous polysaccharide with a relative molecular weight of 7.6×10³ Da， consisting of mannose（Man）， glucose（Glc）， and galactose（Gal） in a molar ratio of 1.3∶23.9∶1.0. It was primarily composed of five sugar residues of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp， and 1，2-α-D-Galp. In vivo experiments showed that compared with the normal group， the model group demonstrated markedly increased DAI score and spleen index， significantly reduced colon length， and significantly elevated levels of TNF-α and IL-6（P<0.01）. Compared with the model group， the AAPS-4a high-dose group significantly reduced the DAI score and spleen index， as well as TNF-α and IL-6 levels， and improved colonic atrophy（P<0.05， P<0.01）. Pathological observations showed that AAPS-4a significantly inhibited inflammatory cell infiltration in colon tissue and alleviated pathological damage. ConclusionAAPS-4a， a neutral homogeneous polysaccharide composed of 1，6-α-D-Glcp， T-α-D-Glcp， 1，3-β-D-Galp， 1，4-α-D-Manp and 1，2-α-D-Galp， is identified as a key bioactive component contributing to the anti-UC effect of the Qi-gui herb pair. Its immunoregulatory and anti-UC properties suggest its potential as a therapeutic agent for UC.

Medicine is the subject of studying human and its inherent humanistic attribute endows medicine with the temperature it deserves. However, with the continuous improvement of medical testing technology and treatment technology, medical workers pay more attention to diseases and ignore humanistic care, which has become an important factor in the aggravation of patients’ burden and the tension relationship between doctors and patients. There are many virtues in Chinese traditional culture. Sun Simiao’s medical ethics thought of "great doctor with professionalism and sincerity" embodies the core value of the humanistic spirit of Chinese traditional medicine. In his medical ethics thought, the moral and ethics of "great doctor with professionalism and sincerity", the medical practice attitude of "being cautious and diligent", the values of "benevolence for the world" and the professional conduct of "honesty and truth" still have strong practical significance at present. It is the good material to cultivate the humanistic spirit of medical students. This is of great value to integrate Sun Simiao’s medical ethics thought into cultivate medical students with both "professionalism" and "sincerity", practice the original intention of medical and health undertakings, and carry forward cultural self-confidence.

Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

Objective:To investigate the changes in synaptic transmission function of hippocampal dentate gyrus granule cells in depression model mice induced by chronic unpredictable mild stress (CUMS) and to explore the effect of exercise on it.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were randomly compartmentalised into control group (CTRL group), model group (CUMS group), model + exercise group (CUMS+ EXE group), and model + fluoxetine group (CUMS+ FLX group), with 12 mice in each group. CUMS method was used for preparating the depression model for 21 d. Mice in the CUMS+ EXE group were given roller locomotion training and mice in the CUMS+ FLX group were given fluoxetine intraperitoneally (10 mg/kg) daily during the modelling period, and the other two groups were administrated intraperitoneally with equal volume of 0.9% NaCl solution.Sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST) were used to detect depressive-like behavior, and open field test (OFT) was used to detect anxiety-like behavior. Whole-cell recordings were used to detect spontaneous excitatory postsynaptic currents (sEPSC), spontaneous inhibitory postsynaptic currents (sIPSC), miniature excitatory postsynaptic currents (mEPSC), and miniature inhibitory postsynaptic currents (mIPSC) in hippocampal dentate gyrus granule cells.One-way ANONA was performed to analyze the data by SPSS 23.0.Results:(1) There were statistically significant differences among the 4 groups of mice in terms of activity time in the center, total distance of OFT and sugar preference rate( F=37.85, 18.41, 28.81 all P<0.01). The activity time in the center((47.81±3.51)s) and total distance((19.63±1.24)m) of OFT and sugar preference rate((55.63±9.11)%) in the CUMS group were lower than those in the CTRL group (all P<0.01), while those in the CUMS+ EXE group((59.87±3.25)s, (23.18±1.24)m, (69.03±8.22)% respectively) were higher than those in the CUMS group (all P<0.05).The sugar preference rate of the CUMS+ EXE group was lower than that in the CTRL group and CTRL+ FLX group (both P<0.01). The differences in immobility time of TST and FST were statistically significant among the 4 groups of mice ( F=113.70, 56.97, both P<0.01). The immobility time of TST and FST of the CUMS group was lower than that of mice in the CTRL group (both P<0.01), while that in the CUMS+ EXE group were lower than that in the CUMS group (both P<0.05) and higher than that in the CTRL group (both P<0.01). (2)There were statistically significant differences in frequency, amplitude and quantification of sEPSC among the 4 groups of mice ( F=22.02, 17.98, 179.00, all P<0.01). The sEPSC frequency, amplitude, and quantification of mice in the CUMS group were lower than those in the CTRL group (all P<0.05), while those in the CUMS+ EXE group were higher than those in the CUMS group (all P<0.05) and lower than those in the CTRL group and CUMS+ FLX group (all P<0.05). The differences in frequency and quantification of sIPSC among the 4 groups of mice were statistically significant ( F=22.12, 184.80, both P<0.01). The sIPSC frequency and quantification of mice in the CUMS group were higher than those in the CTRL group (both P<0.05), while those in the CUMS+ EXE group were lower than those in the CUMS group (both P<0.05) and higher than those in the CTRL group (all P<0.05).The difference in quantification of sEPSC/sIPSC ratios among the 4 groups of mice was statistically significant ( F=267.10, P<0.01). The quantification of sEPSC/sIPSC ratio of mice in the CUMS group was lower than that in the CTRL group ( P<0.05). The quantification of sEPSC/sIPSC ratio of mice in the CUMS+ EXE group was higher than that in the CUMS group ( P<0.05) and lower than that in the CTRL group and CUMS+ FLX group(both P<0.05). (3) The differences in mEPSC frequency and amplitude among the 4 groups of mice were statistically significant ( F=25.07, 23.57, both P<0.01). The mEPSC frequency and amplitude in the CUMS group were lower than those in the CTRL group (both P<0.05), while those in the CUMS+ EXE group were higher than those in the CUMS group (both P<0.05) and lower than those in the CTRL group and CUMS+ FLX group(all P<0.05). The difference in mIPSC frequency among the 4 groups of mice was statistically significant ( F=13.79, P<0.01). The mIPSC frequency of mice in the CUMS+ EXE group was lower than that in the CUMS group ( P<0.05) and higher than that in the CTRL group ( P<0.05). Conclusion:Exercise can partially improve depressive-like behaviours and enhances hippocampus granule cell synaptic transmission in depression model mice.

Objective:To investigate the effects of enriched environment on the behavior of depressive-like mice induced by chronic stress and the synaptic transmission function of hippocampal pyramidal neurons.Methods:Thirty-six 7-week-old SPF grade male C57BL/6J mice were divided into control group, model group and enriched environment group according to the random zone method, with 12 mice in each group.The mice in model group and enriched environment group were subjected to chronic unpredictable mild stress to establish depression models.During the modeling period, the mice in enriched environment group lived in the enriched environment for 6 hours per day, and lived in the routine environment for the rest time just like the mice in control group and model group.The depressive behaviors of mice were detected by sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST).The motor function and anxious behavior of mice were detected by open field test (OFT) and the cognitive function was detected by Morris water maze test.In vitro electrophysiological techniques were used to record field excitatory post-synaptic potentials (fEPSP) in the hippocampus, and whole-cell recording was used to record spontaneous excitatory post-synaptic currents (sEPSC) and miniature excitatory post-synaptic currents (mEPSC) in hippocampal pyramidal neurons.Statistical analysis was conducted by SPSS 23.0 software.Multiple group comparisons of data were conducted by one-way ANOVA and repeated measures ANOVA.Results:(1) Behavioral results showed statistically significant differences among the three groups in terms of total activity time in the central area of OFT, sugar water preference rate of SPT and immobility time of TST and FST ( F=17.12, 26.07, 41.13, 60.18, all P<0.01).The activity time in the central area of OFT and sugar water preference rate of model group were lower than those in the control group (both P<0.01), and the immobility time of TST and FST were higher than those in the control group (both P<0.01).The activity time in the central area of OFT ((56.56±3.47) s) and sugar water preference rate ((71.22±8.37) %) of enriched environment group were higher than those in the model group((52.56±3.47) s, (59.53±8.72)%) (all P<0.05), and the immobility time of TST ((94.19±10.77) s) and FST ((76.98±12.10) s) were lower than those in the model group ((104.58±8.24) s, (111.41±9.56) s)(all P<0.05).(2)The results of spatial learning memory showed that there was a significant difference of group and time interaction effects for latency to find the platform ( F=12.02, P<0.01), and the latency to find the platform in model group was higher than that in control group and enriched environment group (both P<0.01).The results of spatial exploration showed that there were statistically significant differences in the target quadrant residence time and the times crossing the platform among the three groups( F=19.67, 20.27, both P<0.01).The both indexes in the model group were lower than those in control group and enriched environment group (all P<0.01).(3) The results of electrophysiological experiment showed that the interaction effect of fEPSP between groups and stimulations intensity among the three groups was significant( F=1.86, P<0.01).At the stimulation level of 150 mA and 200 mA, the fEPSP of the model group was lower than those of control group and enriched environment group (all P<0.05).(4)The results of the long-term potentiation(LTP) showed a statistically significant difference among the three groups( F=15.32, P<0.01).The LTP of the model group mice ((137.42±4.48)%) was lower than those of the control group ((156.62±4.79)%) and the enriched environment group ((147.86±9.14)%) (both P<0.05).(5) The whole-cell recordings results showed that there was a statistically significant difference in the frequencies of sEPSC and mEPSC among the three groups ( F=15.30, 13.72, both P<0.01).The sEPSC and mEPSC frequencies of the model group mice ((0.60±0.31) Hz, (0.63±0.26) Hz) were lower than those of the control group ((1.27±0.46) Hz, (1.02±0.28) Hz) and the enriched environment group ((0.96±0.45) Hz, (0.83±0.22) Hz) (all P<0.05). Conclusion:Environmental enrichment can alleviate the depressive behaviors induced by chronic stress and enhance cognitive performance, hippocampal pyramidal neuron synaptic transmission and synaptic plasticity in depressive-like mice.

Objective To observe the value of enhanced CT radiomics combined with clinical indicators for predicting of extramural venous invasion(EMVI+)of colorectal cancer.Methods Data of 131 patients with colorectal cancer proved by surgery pathology were retrospectively analyzed.The patients were divided into training set(n=92,including 44 cases with EMVI+ and 48 with EMVI-)and test set(n=39,including 23 cases with EMVI+ and 16 with EMVI-)at the ratio of 7∶3.The best radiomics features were extracted based on preoperative portal-venous phase CT to construct a radiomics model.Univariate and multivariate logistic regression analysis were used to analyze the clinical,CT and pathological data of the training set,and the independent predictors of colorectal cancer EMVI were screened to build a clinical model.Finally a combined model was established based on radiomics and clinical model.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting EMVI+ in colorectal cancer.Calibration curve and decision curve analysis were used to evaluate the calibration degree and clinical practicability of the models.Results Four best radiomics features were selected to construct the radiomics model.Carbohydrate antigen(CA)19-9 and CA 72-4 were both independent predictors of EMVI+ for colorectal cancer(OR=1.033,1.285,both P＜0.05).The AUC of combined model(AUC=0.908)for predicting EMVI+ of colorectal cancer in training set was higher than that of radiomics and clinical models(AUC=0.825,0.770,P=0.017,0.003).In test set,the AUC of radiomics,clinical and combined models was 0.751,0.632 and 0.799,respectively,not being statistical different between each pair(all P＞0.05).The radiomics model and combined model both had good calibration degree.Taken ＞0.1 in training set and ＞0.12 in test set as the thresholds,the clinical net benefit of combined model was higher.Conclusion Enhanced CT radiomics combined with clinical indicators could effectively predict EMVI+of colorectal cancer.

Objective:To summarize the clinical features, electroencephalogram (EEG) and magnetoencephalogram (MEG) of patients with pure paroxysmal kinesigenic dyskinesia (PKD) and PKD with epilepsy, so as to better distinguish them and guide the treatments.Methods:The clinical data of 200 patients diagnosed with PKD in the Outpatient Department of Xuanwu Hospital, Capital Medical University from 2000 to 2023 were analyzed retrospectively. The patients were divided into 2 groups: pure PKD (174 cases) and PKD with epilepsy (26 cases) according to whether accompanied by epilepsy. The differences in clinical features, drug therapy, EEG and MEG were compared between the 2 groups.Results:The clinical features of the 2 groups were essentially similar, and the proportion of PKD dyskinesia induced by emotional stress in the pure PKD group (54/174, 31.03%) was higher than that in the PKD with epilepsy group (2/26, 7.69%; χ 2=5.010, P=0.025). In terms of pharmacological response, carbamazepine was the most commonly used medication in both groups, but patients with PKD with epilepsy may need a higher therapeutic dosages (0.2-0.4 g/d, and gradually increased to 0.8 g/d) to effectively manage both dyskinesia and seizures. Regarding the EEG and MEG, the proportion of EEG abnormalities was higher in PKD patients with epilepsy, mainly manifested as focal spikes [1/70(1.43%) vs 9/21(42.86%), χ 2=24.268, P<0.001], together with aberrant MEG discharge (4/18 vs 3/5, χ 2=1.155, P=0.282). The MEG dipoles were mainly distributed in the brain regions close to the frontal lobe and central region. Conclusions:The clinical manifestations of motor symptoms of pure PKD and PKD with epilepsy are similar, and carbamazepine remains the most effective treatment. PKD patients with epilepsy have a higher proportion of abnormal EEG, mainly manifested as focal spikes, and are more likely to show abnormal discharge of MEG, which could be used to distinguish them.

Objective To investigate the correlation between neuropeptide S receptor(NPSR)single nucleotide polymorphism(SNP)(rs323917,rs323920,rs323922,rs2530547,rs324957)and primary insomnia(PI).Methods A total of 157 patients diagnosed with PI in the outpatient department of Center of Sleep Medicine,Gansu Provincial People's Hospital from December 2016 to May 2019 were selected as PI group,and 133 healthy physical examination subjects during the same period were selected as control group.Venous blood samples were collected and DNA,polymerase chain reaction(PCR)amplification and agarose gel electrophoresis were extracted.rs323917,rs323920,rs323922,rs2530547,rs324957 single nucleotide loci were genotypized by target site sequencing.Meanwhile,standard polysomnosis monitoring was performed to analyze the correlation between gene polymorphism and PI.Results There were no significant differences in the genotype distribution of NPSR SNP sites(rs323917,rs323920,rs323922,rs2530547)and allele frequency and rs324957 allele frequency between two groups(P＞0.05).There was significant difference in genotype distribution of rs324957(P=0.034).There was no significant difference in the frequency of different haplotypes between two groups(P＞0.05).Conclusion The expression of rs324957 SNP genotypes in NPSR may be related to PI,and AG genotype is dominant.

Objective To explore the clinical efficacy of fluoxetine hydrochloride capsules and escitalopram oxalate tablets in the treatment of first-episode depression disorder.Methods Eighty patients with first-episode depression disorder who were hospitalized in the 14th district of Integrated Traditional Chinese and Western Medicine of Xiamen Xianyue Hospital from February to November 2023 were selected,and divided into fluoxetine hydrochloride capsules group(n=40)and escitalopram oxalate tablets group(n=40)according to random number method;Conducted the Hamilton depression scale(HAMD)estimates before treatment and four weeks after treatment,to analyze and compare the clinical efficacy of two groups.Results After four weeks of treatment,the HAMD scores of all patients significantly decreased compared to before treatment in this group(P＜0.01);There was no statistically significant difference between two groups(P＞0.05).There was no statistically significant difference in the total effective rate between two groups(P＞0.05).Conclusion Escitalopram oxalate tablets and fluoxetine hydrochloride capsules were both effective in treatment of the first-episode depression disorder patients,and the total effective rates of them were similar.