ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

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

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

  Objective  To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance.  Methods  Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve.  Results  A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall.  Conclusions  A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Objective To screen small molecule inhibitors of Fusobacterium nucleatum （Fn） based on commercially available compound libraries, and investigate their anti-colorectal cancer activities under Fn intervention in order to obtain novel anti-colorectal cancer lead compounds. Methods The promotion of colorectal cancer proliferation on organoid was validated by Fn. Secondly, the effects of anti-Fn compounds on their in vitro anticancer activity under Fn’s co-incubation with colorectal cancer HCT116 cell were comparative investigated. Finally, in vivo anticancer efficacy of highly active compounds on nude mouse colon cancer HCT116 transplanted tumor under the intervention of Fn was evaluated by gavage. Results Fn could significantly promote the proliferation of rectal cancer organoids. 9 anti-Fn active compounds could significantly enhance their in vitro anticancer activity under Fn’s co-incubation with HCT116 cells. Methotrexate had the strongest anti-cancer activity with IC₅₀ as 0.03 μmol/L. The combined use of methotrexate (0.5 mg/kg) and PD-1 (5.0 mg/kg) had a stronger anti-tumor effect than their standalone use. Conclusion As new small molecule inhibitor of Fn, methotrexate exhibited good in vitro and in vivo anti-colorectal cancer activity against HCT116 cells and nude mouse xenografts under Fn intervention, which showed the foundation for subsequent structural optimization, and could be expected to expand the new indications of methotrexate.

Objective:To explore the effect of Jian-Pi-Zhi-Dong decoction on autonomous activity and dopamine (dopamine, DA) synaptic vesicle protein expression in the striatum of Tourette syndrome (TS) model rats.Methods:The 4-week-old male SD rats were used to establish the TS model by intraperitoneal injection of N-aminodipropionate. Thirty successfully modeled rats were randomly divided into model group, Chinese medicine group, and tiberide group according to random number table method, with 10 rats in each group. And another 10 rats with matched body mass were selected as the control group. Rats in Chinese medicine group were given Jian-Pi-Zhi-Dong decoction solution (1.6 g/100 g) and the rats in tiapride group were given sulfate tiapride suspension (2.1 mg/100 g), while rats in control group and model group were given an equal volume of 0.9% sodium chloride solution, once a day for 4 weeks.The number of autonomous activities in rats was determined by autonomous activity programmer. ELISA was used to detect the level of DA in the striatum of rats and the expression of dopamine transporter (DAT).Vesicular monoamine transporter-2 (VMAT2) and α-synuclein (α-syn) were measured by Western blot.SPSS 25.0 software was used for data analysis. Multiple group comparisons were performed using one-way ANOVA, non-parametric test and repeated measures ANOVA.Results:Comparing the number of autonomous activities among the 4 groups, the interaction effect between time and group was significant ( F=184.354, P<0.001). At the 1-4 weeks of gavaging, the numbers of autonomic activities in the model group were more than those in the control group (all P<0.05).While the numbers of autonomic activities in Chinese medicine group and tiapride group were less than those in the model group (all P<0.05). Moreover, the numbers of autonomic activities in Chinese medicine group and tiapride group from 1 to 4 weeks were less than those after model making (all P<0.05). The Western blot results showed significant differences in the relative expression of α-syn ( H=29.098), DAT ( F=54.632) and VMAT2 ( H=18.982) among the 4 groups (all P<0.001). The expression levels of α-syn protein in Chinese medicine group and tiapride group were both lower than that in the model group (0.39(0.36, 0.51), 0.39(0.36, 0.50), 0.62(0.50, 0.70)) (both P<0.05). The expression level of DAT protein in Chinese medicine group was higher than that in the model group and lower than that in tiapride group ((0.37±0.06), (0.26±0.07), (0.49±0.09)) (both P<0.05). And the expression level of VMAT2 protein in Chinese medicine group had no significant difference compared with that in the model group ( P>0.05).The ELISA results showed significant differences in DA content of striatum among the 4 groups ( F=75.370, P<0.001). The level of DA in the model group was higher than that in the control group ((7.65±0.72) ng/L, (3.71±0.59) ng/L, P<0.05). The levels of DA in Chinese medicine group ((3.92±0.81) ng/L) and tiapride group ((4.40±0.53) ng/L) were lower than that in the model group (both P<0.05), and the difference between Chinese medicine group and tiapride group was not significant ( P>0.05). Conclusion:Jian-Pi-Zhi-Dong decoction can relieve the tic symptoms of the model rats with TS, and its mechanism may be related to inhibiting the excessive release of α-syn, improving the expression of DAT and VMAT2, improving the DA synaptic vesicle circulation, and reducing the DA content in the synaptic space of the brain.

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 explore the relationship among sleep phenotypes, attention deficit and hyperactivity impulsivity (ADHD) symptoms and cognitive information processing in children with ADHD.Methods:A total of 244 children with ADHD aged 6-12 were selected from December 2021 to December 2022.Swanson, Nolan and Pelham rating scale Ⅳ(SNAP-Ⅳ) was used to evaluate the core symptoms of ADHD.Sleep disturbance scale for children (SDSC) was used to evaluate six sleep phenotypes((disorders in initiating and maintaining sleep (DIMS), sleep breathing disorders(SDB), sleep-wake transition disorders(SWTD), disorders of arousal(DA), disorders of excessive somnolence (DOES), and Nocturnal hyperhidrosis(SHY)). Das-Naglieri cognitive function assessment system (DN-CAS) was used to evaluate the cognitive information processing (planning, simultaneous processing, attention and successive processing). Descriptive statistical analysis, Spearman correlation analysis, and mediation analysis were conducted by SPSSAU 23.0 and Zstats software, respectively.Results:Correlation analysis showed that DIMS, SDB, SWTD, DA and DOES were significantly and positively correlated with attention deficit ( r=0.190-0.349, all P<0.01).DIMS(2.14(1.71, 2.57)), SWTD(1.67(1.33, 2.00)) and SHY(2.00(1.50, 3.00)) were significantly positively correlated with hyperactive impulsivity (1.44(1.00, 2.00))( r=0.193, 0.242, 0.133, P<0.05). Attention deficit(1.78(1.44, 2.33)) was significantly and negatively correlated with successive processing(105.00(96.00, 112.00)) ( r=-0.127, P<0.05). The results of multiple linear regression analysis showed that after controlling for sex, age, verbal IQ and operational IQ, DIMS ( β=0.152, P<0.05) and SWTD ( β=0.178, P<0.05) had significant positive predictive effects on hyperactive impulsivity symptoms. DOES ( β=0.259, P<0.01) had significant positive predictive effects on attention deficit symptoms. Attention deficit ( β=-0.183, P<0.05) had a significant negative predictive effect on successive processing. Mediation effect analysis showed that attention deficit played a complete mediating role between DOES and successive processing(effect=-0.179, Bootstrap 95% CI=-0.196--0.110). Conclusion:Different sleep phenotypes are associated with ADHD core symptoms and different dimensions of cognitive information processing processes. DOES indirectly affects successive processing capability by attention deficit symptoms.