ObjectiveTo investigate the mechanism by which Shenqi Yiliu prescription reverses cisplatin resistance in ovarian cancer cells by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway-mediated glycolysis. MethodsThe human ovarian cancer A2780 cell line was intervened with progressively increasing doses of cisplatin （1 g·L^-1） to establish the cisplatin-resistant cell line A2780cisR， and the cell sensitivity to cisplatin was examined by the cell counting kit-8 （CCK-8） assay. High， medium， and low （39.9， 19.95， 9.98 g·kg^-1） doses of Shenqi Yiliu prescription-containing sera were used to treat A2780cisR cells for 48 h. Glucose consumption and lactate production were measured by the cuvette assay. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the activities of glucose transporter （GLUT）， phosphofructokinase （PFK）， and pyruvate kinase （PK）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect apoptosis. Western blot was employed to quantify the protein levels of phosphorylated （p）-PI3K， p-Akt， p-mTOR， hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， B-cell lymphoblastoma-2 （Bcl-2）， Bcl-2-associated X-protein （Bax）， and B-lymphoblastoma-2 gene-related promoter （Bad）. Real-time PCR was conducted to determine the mRNA levels of HK2， PKM2， Bax， Bcl-2， and Bad. ResultsThe median inhibitory concentration （IC₅₀） of cisplatin on A2780cisR cells was nearly 3 times that on A2780P cells. Compared with A2780P cells， A2780cisR cells showed increased glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax （P<0.05）， and decreased apoptosis rate and Bcl-2 expression （P<0.05）. Compared with A2780cisR cells， medium- and high-dose Shenqi Yiliu prescription reduced the glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax， and Bad （P<0.05）， while increasing the apoptosis rate and Bcl-2 expression （P<0.05）. ConclusionShenqi Yiliu prescription can inhibit glycolysis mediated by the PI3K/Akt/mTOR pathway to promote apoptosis， thereby reversing cisplatin resistance in ovarian cancer cells.

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

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.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

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.

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.