BACKGROUND:Mechanical stimulation has been confirmed to promote osteogenic differentiation of bone marrow stromal stem cells,but the mechanism is unknown.Primary cilia are important mechanoreceptors and regulate various signaling pathways such as TGF-β1/BMP-2/SMAD.They are likely to be important targets for mechanical regulation of bone marrow stromal stem cells. OBJECTIVE:To investigate the effect and mechanism of fluid shear stress on osteogenic differentiation of bone marrow stromal stem cells. METHODS:Rat bone marrow stromal stem cells were divided into control group,mechanical stimulation group(fluid shear mechanics intervention by shaking table),mechanical stimulation + IFT88 silencing group(mechanical stimulation + silencing IFT88 expression with siRNA).After 24 hours of intervention,qRT-PCR was utilized to determine the expression of transforming growth factor β1 and bone morphogenetic protein 2.Western blot assay was used to detect the expression of phosphorylated SMAD2/3 protein.Immunofluorescent staining of primary cilia was conducted and morphology was analyzed. RESULTS AND CONCLUSION:Shear stress stimulation could promote the transcriptional activity of transforming growth factor β1 and bone morphogenetic protein 2 genes,and increase the expression of phosphorylated SMAD2/3 protein.After siRNA interfered with primary cilia,this mechanical response effect was significantly reduced.There was a Spearman correlation between the change ratio of the primary cilium area of bone marrow stromal stem cells and the increased ratio of transforming growth factor β1 and bone morphogenetic protein 2 gene transcription.These findings indicate that primary cilia/intraflagellar transport mediates the activation of fluid shear stress-responsive transforming growth factor β1/bone morphogenetic protein 2/SMAD signaling pathway and promotes osteogenic differentiation of bone marrow stromal stem cells.

BACKGROUND:Cervical neutral position magnetic resonance imaging is widely used for the diagnosis and treatment of cervical spondylotic myelopathy.However,it is not possible for patients to maintain the exact same position of the head and neck during repeated cervical magnetic resonance imaging examinations.The cervical spine undergoes minor flexion and extension movements in the sagittal plane,and the head may have a certain degree of variation in flexion and extension.Whether these changes in the neutral position of the cervical spine affect the volume of cervical discs herniation and cervical curvature is unclear. OBJECTIVE:Using artificial intelligence-assisted measurement,this study aimed to analyze the accuracy and reliability of magnetic resonance imaging examinations for measuring the volume of cervical discs herniation and cervical curvature in patients with cervical spondylotic myelopathy undergoing two consecutive cervical neutral positions in the short term. METHODS:A retrospective study was conducted on patients with cervical spondylotic myelopathy who underwent conservative treatment and underwent two consecutive cervical magnetic resonance imaging examinations within three months between June 2012 and June 2023.We proposed the use of occipital-thoracic distance and occipital-thoracic angle to evaluate the variation in flexion and extension of the head in the neutral position of the cervical spine.Based on the changes in occipital-thoracic angle,patients were divided into occipital-thoracic angle increase group and occipital-thoracic angle decrease group.Cervical discs herniation volume,C2-6 Cobb angle,and cervical(C3-C7)curvature were measured using artificial intelligence-assisted measurement software.Normal distribution data were represented by mean±SD,while non-normal distribution data were represented by the median(interquartile range).Spearman's rank correlation coefficient was used to analyze the correlation between changes in Cobb angle,cervical(C3-C7)curvature,and cervical discs herniation volume. RESULTS AND CONCLUSION:(1)A total of 104 patients and 326 cervical discs herniation were included in the study.There were 47 patients in the occipital-thoracic angle increase group and 57 patients in the occipital-thoracic angle decrease group.(2)Extension and flexion index of the head:There were no significant differences in occipital-thoracic distance and occipital-thoracic angle during the initial diagnosis and follow-up examination.The variation of occipital-thoracic distance was 0.035(3.23)mm,and the variation of occipital-thoracic angle was-0.31(3.28)°.The deviation range of occipital-thoracic distance and occipital-thoracic angle was small,and there was no significant correlation.(3)Cervical curvature index:There were no significant differences in C2-6 Cobb angle and C3-C7 curvature during the initial diagnosis and follow-up examination.There were no significant differences in C2-6 Cobb angle and C3-C7 curvature between the occipital-thoracic angle increase group and occipital-thoracic angle decrease group.(4)There was no significant difference in volume of cervical discs herniation during the initial diagnosis and follow-up examination.There was no significant difference in volume of cervical discs herniation between the occipital-thoracic angle increase group and occipital-thoracic angle decrease group.There was no significant correlation between the change of cervical discs herniation volume and the change of C2-6 Cobb angle and the cervical(C3-C7)curvature.(5)These results indicate that in the neutral position of the cervical spine,there were negligible minor flexion and extension movements in the sagittal plane,and the head was limited to a specific position.Although the head has a certain range of flexion and extension variation,it does not affect the accuracy and reliability of parameters including cervical discs herniation volume,C2-6 Cobb angle,and cervical(C3-C7)curvature.

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Background: in vitro culture of preantral follicles is a promising technology for fertility preservation. Objectives: This study aims to investigate an optimized three-dimensional (3D) fetal bovine serum (FBS)-free preantral follicle culture system having a simple and easy operation. Methods: The isolated follicles from mouse ovaries were randomly divided in an ultra-low attachment 96-well plates supplement with FBS or bovine serum albumin (BSA) culture or encapsulated with an alginate supplement with FBS or BSA culture. Meanwhile, estradiol (E 2 ) concentration was assessed through enzyme-linked immunosorbent assay of culture supernatants. The diameter of follicular growth was measured, and the lumen of the follicle was photographed. Spindle microtubules of oocytes were detected via immunofluorescence.The ability of oocytes to fertilize was assessed using in vitro fertilization. Results: The diameters were larger for the growing secondary follicles cultured in ultra-low attachment 96-well plates than in the alginate gel on days 6, 8, and 10 (p < 0.05). Meanwhile, the E 2 concentration in the BSA-supplemented medium was significantly higher in the alginate gel than in the other three groups on days 6 and 8 (p < 0.05), and the oocytes in the FBS-free system could complete meiosis and fertilization in vitro. Conclusions The present study furnishes insights into the mature oocytes obtained from the 3D culture of the preantral follicle by using ultra-low attachment 96-well plate with an FBSfree system in vitro and supports the clinical practices to achieve competent, mature oocytes for in vitro fertilization.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.

OBJECT IVE To evaluate the application effect of the whole cour se medication management mode led by pharmacists in rheumatic immune diseases. METHODS A total of 122 patients treated with tacrolimus or cyclosporine in the department of rheumatology and immunology of Wuhan No. 1 Hospital from 2018 to 2020 were selected as the study subjects. Among them ，44 cases in the control group were under the traditional supervision mode ；78 patients in the observation group adopted the whole course medication management mode led by pharmacists ，that was ，individual pharmacists and specialist clinical pharmacists cooperated and led ，and not only participated in the whole process of drug treatment but also involved in the whole process of therapeutic drug monitoring （TDM）. On the basis of the control group ，the division of labor and cooperation among medical，pharmaceutical and nursing parties were strengthened ，and the homogeneous supervision was carried out for the outpatients and inpatients from admission to discharge . The daily dose of medication ，the rate of reaching the standard of blood drug concentration ，the incidence of problematic samples （the sample was calculated by the number of times ），the average hospitalization days ，the re-admission rate within 6 months after discharge ，the medication compliance score and the patient ’s satisfaction rate were compared between the two groups. RESULTS In the control group ，53 times of TDM were performed ， including 18 times of tacrolimus monitoring and 35 times of cyclosporine monitoring ；in the observation group ，123 timesof TDM were performed ，including 55 times of tacrolimus monitoring and 68 times of cyclosporine monitoring. The daily dose of tacrolimus ，the daily dose of cyclosporine ，the rate of reaching the standard of cyclosporine blood drugconcentration，the inc idence of problematic samples ，the rate of re-admission within 6 months after discharge ， the medication compliance score and the patient ’s satisfaction rate in the observation group were significantly better than those in the control group （P＜0.05）. CONCLUSIONS It can effectively improve the effect of the quality of pharmaceutical care to implement whole course and homogeneous medication management led by pharmacists and provide precise drug guidance for patients with rheumatic and immune diseases.

OBJECTIVE：To investigate the effects of integrated su pervision mode by doctors ，pharmacists and nurses on the whole-process implementation of therapeutic drug monitoring （TDM）. METHODS ：The patients monitored with TDM in our hospital admitted from Jan. to Dec. 2018 were selected as control group ，treated with the traditional drug supervision mode （i.e. the work of doctors ，nurses and pharmacists was relatively independent ）. Treatment group was composed of inpatients monitored with TDM from Jan. to Dec. 2019，treated with the integrated supervision mode of doctors ，nurses and pharmacists （i.e. doctors ，nurses and pharmacists cooperated with each other ，taking the patients and sample as the center ，pharmacists as the key link formulated the implementation standards of each link ，and clarified their respective responsibilities ）. The concentration compliance rate ，the incidence of incorrect samples ，critical value notification rate ，clinical satisfaction ，drug recommendation feedback and adoption ， compliance rates of 6 kinds of monitored drugs （sodium valproate ，digoxin，tacrolimus，cyclosporin，methotrexate，vancomycin） were compared between two groups. RESULTS ：The overall compliance rate ，critical value notification rate and clinical satisfaction rate of the observation group were respectively 64.57％，99.39％ and 97.22％，which were significantly higher than 57.86％， 96.80％ and 92.22％ of control group （P＜0.05）. The incidence of incorrect samples in observation group was 0.72％，which was significantly lower than 3.09％ of control group （P＜0.001）. The feedback rate of individual pharmacists （89.19％），the feedback rate of doctors （80.50％）and the adoption rate of medication suggestions （69.98％）in the observation group were significantly higher than control group （50.34％ ，71.46％ and 55.36％ ，P＜0.001）. The compliance rate of tacrolimus concentration in observation group was slightly lower than control group （73.40％ vs 75.77％，P＞0.05）. The concentration compliance rate of other 5 varieties was higher than control group ，and the differences of valproate sodium ，digoxin and vancomycin concentrations between two groups were statistically significant （P＜0.05）. CONCLUSIONS ：The implementation of integrated doctors ，nurses and pharmacists supervision mode in TDM can effectively improve the drug concentration compliance rate ，realize the . dynamic supervision and feedback of individualized drug use ， which is conducive to ensure the safety of clinical medication.

Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. Materials and Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signedrank test were performed to compare the objective measurements and the subjective image quality scores, respectively. Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, p > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. Conclusion The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.

Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. Materials and Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signedrank test were performed to compare the objective measurements and the subjective image quality scores, respectively. Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, p > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. Conclusion The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.