Objective To investigate the molecular mechanism by which high mobility group box 1 (HMGB1) mediates renal tubular epithelial cell injury in a high-calcium environment. Methods A CaCl_2 concentration gradient (0, 0.5, 1, 2 mg/mL) treatment system was established based on human renal tubular epithelial cells (HK-2 cells). The calcium ioninduced cell injury effects were evaluated with CCK-8 assay, lactate dehydrogenase (LDH) detection, and DAPI staining. The optimal CaCl_2 concentration was selected for subsequent experiments. The secretion level of HMGB1 in the cell supernatant was detected with ELISA, and the expressions of autophagy markers (LC3-Ⅱ/LC3-Ⅰ, p62) and mTOR pathway-related proteins were detected with Western blot. Lentiviral-mediated HMGB1 silencing (shHMGB1) or pretreatment with ethyl pyruvate (EP), a specific inhibitor of HMGB1, was used on HK-2 cells to verify the role of HMGB1 in cell injury. Additionally, the autophagy agonist rapamycin was added to further clarify the role of the mammalian target of rapamycin (mTOR) signaling axis. Results Different concentrations of CaCl_2 promoted the release of HMGB1, activated autophagy, induced renal tubular epithelial cell injury, increased LDH release, and exacerbated nuclear damage. The optimal concentration was 1 mg/mL in the follow-up experiment. Targeted inhibition of HMGB1 significantly alleviated CaCl_2-induced autophagic response and cell injury. The underlying mechanism might involve the inhibition of HMGB1 expression leading to the blockage of the downstream mTOR signaling pathway, thereby preventing excessive autophagy activation.Conclusion The high-calcium environment activates autophagy through the HMGB1/mTOR signaling axis, which may be one of the important mechanisms by which hypercalciuria promotes renal tubular epithelial cell injury.

Objective:To investigate the function and mechanism of exosomes in bladder cancer cell growth and metastasis regulating by NETs.Methods:The exosomes secreted by SV-HUC-1,MGH-U3 and 253J cells were extracted.PBS and the above exo-somes incubated with PMN,recorded as PBS group,SV-HUC-1 exo group,MGH-U3 exo group,253J exo group.The generation of NETs was detected by Sytox green staining,and the expressions of NETs marker proteins CIT-H3,NE and MPO were detected by Western blot.MGH-U3 and 253J cells were divided into Control group,PMN group,MGH-U3 exo group,253J exo group MGH-U3 exo+PMN group,253J exo+PMN group.The PMN culture supernatant of MGH-U3 exo group and 253J exo group were added with 1.5 U/ml DNAse,after incubation for 30 min,the collected mixture to co-incubate with MGH-U3 and 253J cells,recorded as MGH-U3 exo+PMN+DNAse group and 253J exo+PMN+DNAse group.The proliferation ability of MGH-U3 and 253J cells were detected by CCK8,the migration and invasion of cells were detected by Transwell,and the phosphorylation levels of PI3K and AKT were detected by Western blot.Results:Compared with PBS group,the formation of NETs and the expressions of CIT-H3,NE and MPO in MGH-U3 exo group and 253J exo group increased significantly(P<0.001).There was no significant change of the above indexes in SV-HUC-1 exo group.Compared with Control group,MGH-U3 exo+PMN group and 253J exo+PMN group had significantly increased cell prolifer-ation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT increased significantly(P<0.001).Com-pared with MGH-U3 exo+PMN group,MGH-U3 exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT decreased significantly(P<0.001).Compared with 293J exo+PMN group,293J exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability,the phosphor-ylation levels of PI3K and AKT decreased significantly(P<0.001).Conclusion:The exosomes of bladder cancer cells can promote the proliferation,migration and invasion of tumor cells by inducing the generation of NETs.

At present, the C-arm structure accelerators commonly used in radiotherapy equipment are complex in operation and have potential safety hazards when realizing non-coplanar treatment. By combining with medical robotic arm technology, a spherical radiotherapy accelerator motion system is designed. The beam module is clamped by the medical robotic arm structure to achieve three-dimensional multi-angle irradiation treatment within the non-coplanar angle range. Firstly, the rotating mechanism, beam module, and MLC module of the spherical radiotherapy equipment are designed. Then, the double-plane counterweight method is used to calculate the dynamic balance of the equipment, ensuring that the beam center point does not rotate during the treatment process. Finally, the strength check and reliability analysis of the transmission component gear are conducted. The results show that the designed spherical radiotherapy accelerator motion system can meet the requirements of stable, accurate, and fast precision radiotherapy, which is conducive to improving the treatment efficiency.
Particle Accelerators/instrumentation* ; Equipment Design ; Reproducibility of Results ; Radiotherapy/instrumentation*

Objective:To explore the clinical value of the three-dimensional fat suppression fast spoiled gradient echo (3D-FS-FSPGR) MRI sequence in the preoperative evaluation of congenital radial polydactyly.Methods:The data of children with congenital radial polydactyly who underwent surgical treatment in the Department of Orthopedics at Shanxi Children’s Hospital from May 2021 to April 2022 were retrospectively analyzed. Preoperative X-ray examinations and MRI 3D-FS-FSPGR sequence scans were performed on the children. Radiologists first described the morphological characteristics of the articular cartilage, and then orthopedic surgeons performed the Wassel classification based on the X-ray and MRI imaging result, focusing on the bifurcation level, morphology, and articular surface of the phalangeal and metacarpal cartilage. The corresponding surgical method was selected according to the Wassel classification, and intraoperative incision exploration was used as the gold standard. Six months after surgery, the surgical outcome was evaluated using the modified Tada scoring system [with a total score of 0-7, and classified as excellent: >5 points, good: 3-5 points, and poor: <3 points; the excellent and good rate = (excellent + good) cases/total number of cases × 100%]. The appearance, function and recurrence of the operated finger were evaluated 1 year after surgery. Descriptive statistics were performed using SPSS 26.0 software, and the Kappa coefficient was used to evaluate the consistency of the Wassel classification result between radiographs, MRI 3D-FS-FSPGR sequences and intraoperative exploration respectively.Results:A total of 45 children (55 fingers) with congenital radial polydactyly were enrolled, including 25 males and 20 females, aged 5 to 60 months, with the median age of 9 months. Unilateral findings were seen in 35 cases and bilateral findings in 10 cases. MRI 3D-FS-FSPGR imaging sequences clearly demonstrated the level of cartilage bifurcation and bone tissue growth and development, which were consistent with intraoperative exploration findings. The accuracy of the MRI 3D-FS-FSPGR Wassel classification was 100% (55/55), and the accuracy of the X-ray Wassel classification was 81.8% (45/55). Disagreements were found in the classifications of five fingers: three with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅲ, and two with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅴ. The Kappa coefficients were all >0.85. All patients were followed up for 1 year. The modified Tada score showed excellent in 41 fingers, good in 6 fingers, and poor in 8 fingers, for an excellent and good rate of 85.5% (47/55). At final follow-up, the reconstructed thumbs showed significant improvement in appearance, with normal bone axis restoration, no deviation of the digits, and normal nail appearance. There was no significant scarring or contracture. Functions of thumb flexion, extension, grasping, and opposition were good. There was no postoperative deformity or recurrence.Conclusion:MRI 3D-FS-FSPGR sequences can accurately classify congenital radial polydactyly preoperatively, optimize the surgical incision and osteotomy alignment, and achieve excellent surgical outcomes.

Objective:To explore the clinical value of the three-dimensional fat suppression fast spoiled gradient echo (3D-FS-FSPGR) MRI sequence in the preoperative evaluation of congenital radial polydactyly.Methods:The data of children with congenital radial polydactyly who underwent surgical treatment in the Department of Orthopedics at Shanxi Children’s Hospital from May 2021 to April 2022 were retrospectively analyzed. Preoperative X-ray examinations and MRI 3D-FS-FSPGR sequence scans were performed on the children. Radiologists first described the morphological characteristics of the articular cartilage, and then orthopedic surgeons performed the Wassel classification based on the X-ray and MRI imaging result, focusing on the bifurcation level, morphology, and articular surface of the phalangeal and metacarpal cartilage. The corresponding surgical method was selected according to the Wassel classification, and intraoperative incision exploration was used as the gold standard. Six months after surgery, the surgical outcome was evaluated using the modified Tada scoring system [with a total score of 0-7, and classified as excellent: >5 points, good: 3-5 points, and poor: <3 points; the excellent and good rate = (excellent + good) cases/total number of cases × 100%]. The appearance, function and recurrence of the operated finger were evaluated 1 year after surgery. Descriptive statistics were performed using SPSS 26.0 software, and the Kappa coefficient was used to evaluate the consistency of the Wassel classification result between radiographs, MRI 3D-FS-FSPGR sequences and intraoperative exploration respectively.Results:A total of 45 children (55 fingers) with congenital radial polydactyly were enrolled, including 25 males and 20 females, aged 5 to 60 months, with the median age of 9 months. Unilateral findings were seen in 35 cases and bilateral findings in 10 cases. MRI 3D-FS-FSPGR imaging sequences clearly demonstrated the level of cartilage bifurcation and bone tissue growth and development, which were consistent with intraoperative exploration findings. The accuracy of the MRI 3D-FS-FSPGR Wassel classification was 100% (55/55), and the accuracy of the X-ray Wassel classification was 81.8% (45/55). Disagreements were found in the classifications of five fingers: three with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅲ, and two with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅴ. The Kappa coefficients were all >0.85. All patients were followed up for 1 year. The modified Tada score showed excellent in 41 fingers, good in 6 fingers, and poor in 8 fingers, for an excellent and good rate of 85.5% (47/55). At final follow-up, the reconstructed thumbs showed significant improvement in appearance, with normal bone axis restoration, no deviation of the digits, and normal nail appearance. There was no significant scarring or contracture. Functions of thumb flexion, extension, grasping, and opposition were good. There was no postoperative deformity or recurrence.Conclusion:MRI 3D-FS-FSPGR sequences can accurately classify congenital radial polydactyly preoperatively, optimize the surgical incision and osteotomy alignment, and achieve excellent surgical outcomes.

Objective:To investigate the function and mechanism of exosomes in bladder cancer cell growth and metastasis regulating by NETs.Methods:The exosomes secreted by SV-HUC-1,MGH-U3 and 253J cells were extracted.PBS and the above exo-somes incubated with PMN,recorded as PBS group,SV-HUC-1 exo group,MGH-U3 exo group,253J exo group.The generation of NETs was detected by Sytox green staining,and the expressions of NETs marker proteins CIT-H3,NE and MPO were detected by Western blot.MGH-U3 and 253J cells were divided into Control group,PMN group,MGH-U3 exo group,253J exo group MGH-U3 exo+PMN group,253J exo+PMN group.The PMN culture supernatant of MGH-U3 exo group and 253J exo group were added with 1.5 U/ml DNAse,after incubation for 30 min,the collected mixture to co-incubate with MGH-U3 and 253J cells,recorded as MGH-U3 exo+PMN+DNAse group and 253J exo+PMN+DNAse group.The proliferation ability of MGH-U3 and 253J cells were detected by CCK8,the migration and invasion of cells were detected by Transwell,and the phosphorylation levels of PI3K and AKT were detected by Western blot.Results:Compared with PBS group,the formation of NETs and the expressions of CIT-H3,NE and MPO in MGH-U3 exo group and 253J exo group increased significantly(P<0.001).There was no significant change of the above indexes in SV-HUC-1 exo group.Compared with Control group,MGH-U3 exo+PMN group and 253J exo+PMN group had significantly increased cell prolifer-ation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT increased significantly(P<0.001).Com-pared with MGH-U3 exo+PMN group,MGH-U3 exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT decreased significantly(P<0.001).Compared with 293J exo+PMN group,293J exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability,the phosphor-ylation levels of PI3K and AKT decreased significantly(P<0.001).Conclusion:The exosomes of bladder cancer cells can promote the proliferation,migration and invasion of tumor cells by inducing the generation of NETs.

Objective:To investigate the application of CT image omics model in the differential diagnosis of ganglioneuroblastoma (GNB) and neuroblastoma (NB) in childhood.Methods:A retrospective case series study was performed. The clinical and imaging data of 23 NB and 23 GNB pediatric patients confirmed by surgery and pathology in Shanxi Children's Hospital from January 2013 to December 2013 were collected. The original CT images in the normal scan phase, arterial phase and venous phase of all the children before operation were extracted from the PACS system in DICOM format. ITK-SNAP (ver.3.4.0) software was applied to manually outline and extract the image omics features layer by layer of the lesions in the normal scan phase, arterial phase and venous phase of each patient before surgery. The minimum absolute contraction selection operator and stepwise multi-factor logistic regression method were used to screen out effective features in different scan phases. The corresponding phase image omics model was established by using logistic model. The diagnostic efficiency of each phase of the image omics model was evaluated by using the receiver operating characteristic curve, calibration curve and decision curve.Results:A total of 1 361 image omics features were extracted from the original CT images in the 3 phases. The model was established by using multi-factor logistic regression to extract 4 features in the normal scan phase, 2 features in the arterial phase, 3 features in the venous phase and 7 features in the combination of the 3 phases. The area under the curve (AUC) of the model in the normal scan phase was 0.940, the accuracy was 89.1%, the sensitivity was 91.3% and the specificity was 87.0%; the AUC of the model in the arterial phase was 0.923, the accuracy was 84.8%, the sensitivity was 82.6%, and the specificity was 87.0%; the AUC of the model in the venous phase was 0.949, the accuracy was 87.8%, the sensitivity was 83.3%, and the specificity was 91.3%; the AUC of 3 phases combined model was 0.964, the accuracy was 95.1%, the sensitivity was 94.7%, and the specificity was 95.5%. The results showed that the single-phase image omics model was effective in the differential diagnosis of NB and GNB in childhood; the AUC, accuracy, sensitivity and specificity of the 3 phases combined imaging model were higher than those of the single-phase imaging model. The calibration curve and decision curve showed that the probability of differential diagnosis of NB and GNB in childhood by the 3 phases combined model had a high consistency with the observed value, and a good net benefit could be achieved.Conclusions:CT-based image omics model has a high clinical value in the differential diagnosis of NB and GNB in childhood.

Objective:To investigate the risk factors of white matter damage（WMD）in premature infants，especially intraventricular hemorrhage（IVH）.Methods:This retrospective study included 639 premature infants admitted to the neonatal intensive care unit of Shanxi Children's Hospital from June 2022 to June 2023.The premature infants were divided into WMD group（145 cases）and control group（494 cases）according to the results of head MRI.Univariate analysis and multivariate logistic regression analysis were used to explore the risk factors for WMD in premature infants.Results:There were no significant differences in gender，gestational age，fetal distress，cesarean section，asphyxia，Apgar 1min，umbilical artery pH，maternal age，number of pregnancy，infants of assisted reproductive technology，gestational hypertension，gestational diabetes mellitus，acute chorioamnionitis and prelabor rupture of membranes between the two groups（all P>0.05）.Compared the WMD group with the control group，birth weight［（1 571±611）g vs（1 438±489）g， t=-2.393］，umbilical artery base excess［-5.9（-8.2，-3.9）mmol/L vs -5.3（-7.2，-3.5）mmol/L， Z=-2.538］，umbilical artery lactate［3.7（2.4，5.3）mmol/L vs 2.8（2.0，4.1）mmol/L， Z=-4.607］，sepsis（28.5% vs 15.6%， χ 2=12.280），patent ductus arteriosus（82.6% vs 74.7%， χ 2=3.911），hypocarbia（57.2% vs 45.0%， χ 2=6.696），invasive ventilation（75.9% vs 53.0%， χ 2= 24.010），multifetal pregnancy（19.3% vs 30.6%， χ 2=7.111），antenatal corticosteroids（51.0% vs 61.9%， χ 2=5.451），lowest PaCO 2 value［（28.4±6.7）mmHg vs（31.4±8.0）mmHg， t=4.471］were different significantly（all P<0.05）.There was significant difference in the distribution of IVH between the two groups（ χ 2 =40.015， P<0.01）and multiple comparisons showed that the proportion of grade Ⅲ-Ⅳ IVH in the WMD group was higher than that in the control group（ P<0.05）.Multiple logistic regression analysis showed that umbilical artery lactate，grade Ⅲ-Ⅳ IVH，sepsis and invasive ventilation were high risk factors of WMD，and multifetal pregnancy was protective factor of WMD，with OR（ 95%CI）1.121（1.023，1.228），11.435（3.925，33.314），1.758（1.064，2.904），1.640（1.004，2.680），and 0.587（0.358，0.962），respectively. Conclusions:Umbilical artery lactate，grade Ⅲ-Ⅳ IVH，sepsis，and invasive ventilation are independent risk factors for WMD.

Objective:To analyze the expression of MXD1 and Ki-67 in breast invasive ductal carcinoma (IDC) and their relationship with clinicopathologic features.Methods:Clinical data of 68 patients with breast invasive ductal carcinoma admitted to Shanxi Maternal and Child Health Hospital and Shanxi Cancer Hospital from Mar. 2022 to Mar. 2023 were retrospectively analyzed,and the expressions of MXD1 and Ki67 in cancer tissues and adjacent normal tissues of patients with breast invasive ductal carcinoma were measured. The expressions of MXD1 and Ki67 in cancer tissues of patients with different clinicopathological characteristics were analyzed. The relationship between the expression of MXD1 and Ki67 and clinicopathological features; Follow-up until March 2024 was conducted to analyze the survival of different expressions of MXD1 and Ki67.Results:The high expression of MXD1 and positive Ki67 in cancer tissues of 68 patients were 63.24% and 69.12%, respectively, which were significantly higher than 8.82% and 11.76% in normal tissues ( χ2=43.67, 46.43, P<0.05). The proportion of high expression of MXD1 and Ki67 positive in histological grade Ⅲ, low differentiation, TNM stage Ⅲ or Ⅳ was significantly higher than that in histological grade Ⅰ or Ⅱ, middle and high differentiation, TNM stage Ⅰ or Ⅱ ( χ2=4.05, 5.87, 6.00, 4.00, 5.78, 5.39, P<0.05). The expressions of MXD1 and Ki67 were positively correlated with histological grade and TNM stage, and inversely correlated with differentiation degree ( r=0.34, 0.39, 0.39, 0.38, -0.39, -0.34, P<0.05). The survival curves of different expressions of MXD1 and Ki67 were statistically significant (Log-Rank χ2=10.13,10.72, P<0.05). At the end of follow-up,the median survival time of low and high expression of MXD1 was 17 months (95% CI: 15.059-18.941) and 14 months (95% CI: 12.452-15.548), respectively, and the median survival time of negative and positive expression of Ki67 was 19 months (95% CI: 13.335-24.665), 14 months (95% CI: 12.432-15.568) . Conclusion:MXD1 is highly expressed and Ki67 positiverate is higher in patients with breast invasive ductal carcinoma, which is related to histological grade, TNM stage, differentiation degree and survival time.

To investigate the molecular mechanism of modified Yigong powder(MYG)in the treat-ment of spleen deficiency syndrome based on network pharmacology and analyzed the effect of MYG on gastrointestinal simulated intestinal flora of spleen deficiency dogs and mucosal barrier of Caco-2 cells,as well as the interaction between intestinal flora and mucosal barrier.The molecular mechanism of MYG in the treatment of spleen deficiency syndrome was predicted by network pharmacology.The fecal samples of three canines(12±1)years old with spleen deficiency were collected to establish an in vitro gastrointestinal simulation system,which was divided into the o-riginal fecal sample group,the gastrointestinal simulation group and the gastrointestinal simulation treated by MYG group.The structural changes of the flora in each group were detected by 16S rD-NA sequencing.The metabolites were extracted from the gastrointestinal simulation system trea-ted by MYG group to study its effect on LPS-induced Caco-2 cell mucosal barrier injury model.The cell experiments included the blank control group,LPS model group,modified Yigong metabolite group.The permeability of mucosal was determined by fluorescein sodium,and then relative ex-pression levels of Claudin-1,Occludin and ZO-1 mRNA were determined by qPCR.The correlation between intestinal flora and Caco-2 cell mucosal barrier index after MYG intervention was further analyzed.The results showed that MYG had 76 active ingredients and 45 potential targets for the treatment of spleen deficiency syndrome.Forty key targets were obtained through protein interac-tion analysis,34 items were obtained by GO enrichment analysis,and 16 pathways were obtained by KEGG enrichment analysis.In the gastrointestinal simulation system,compared with the gas-trointestinal simulation group,at the phylum level,the abundance of Firmicutes,Bacteroides and Actinobacteriota increased significantly(P＜0.05),and the abundance of Proteobacteria decreased significantly(P＜0.05).At the genus level,the abundance of Fusobacterium,[Ruminococcus]gna-vus group and Blautia increased significantly(P＜0.05),while the abundance of Escherichia-Shi-gella and Citrobacter decreased significantly(P＜0.05).The diversity index of intestinal flora in the gastrointestinal simulation treated by MYG group was significantly increased(P＜0.05).In cell experiments,compared with the LPS model group,the mucosal permeability of Caco-2 cells in the modified Yigong metabolite group was significantly reduced(P＜0.01),and the expression levels of Claudin-1,Occludin and ZO-1 mRNA were significantly increased(P＜0.01).Correlation analysis showed that there was a certain correlation between bacterial community structure and mucosal barrier indexes.In summary,MYG may act on 40 key targets such as TNF,IL6,IL18,CX-CL8 and AKT1 through 76 active ingredients such as quercetin,arachidonic acid and naringin,and treat spleen deficiency syndrome in dogs through 16 signaling pathways such as AGE-RAGE,FoxO and HIF-l.In addition,the gastrointestinal metabolites of MYG up-regulate tight junction protein mRNA expression,reduce mucosal permeability,and repair mucosal barrier,which may be related to MYG's regulation of flora structure.