BACKGROUND:Micro-robots have the characteristics of small size,flexibility,and strong targeting,and can complete complex tasks in a single or clustered manner in a narrow environment.With the continuous optimization of materials,preparation processes,and driving approaches,they have shown increasingly important application value in the field of biomedicine. OBJECTIVE:To analyze the application of field-driven micro-robots in medical field and to look forward to their application prospect. METHODS:Using"microrobots,nanorobots,drivers,biomedical,medical"as Chinese keywords and"microrobots,micro-robots,nanorobots,micromachine,microswimmer,medical"as English keywords,WanFang Data and PubMed databases were searched,respectively.The search time range was from January 2010 to January 2024,and a small number of long-term articles were included.Through reading the titles and preliminarily screening the abstracts,the repetitive studies,low-quality journals,and irrelevant literature were excluded.After reading the entire text,66 papers were finally included for review. RESULTS AND CONCLUSION:Field-driven medical micro-robots mainly include magnetic,optical,thermal,ultrasonic,and multi-mixed factor-driven robots.Field-driven robots have been used in intestinal diagnosis,drug targeting therapy,and stem cell therapy.Medical micro-robots are currently only used in a small number of clinical applications,but most of which are still in the theoretical and experimental stages.Medical micro-robots will face many challenges in future,such as large-scale preparation,precise control of micro-robots,recycling or degradation in vivo,whether the materials used will cause adverse reactions to the human body,and the related minimally invasive medical procedures.

Objective:To analyze the correlation between serum calcium levels and the prognosis of survival and renal recovery in patients with acute kidney injury (AKI) accompanied by hypercalcemia.Methods:This retrospective study analyzed the clinical data of patients with AKI accompanied by hypercalcemia admitted to Shanghai General Hospital from December 2015 to August 2022. There were 157 patients included in the study. The observation endpoint was set at discharge, focusing on the patients' survival and renal recovery during this period. Based on their status at discharge, patients were divided into a survival group (116 cases) and a death group (41 cases); and among the survivors, into a renal recovery group (63 cases) and a non-recovery group (53 cases). Continuous variables conforming to normal distribution were expressed as xˉ± s, and the mean comparison between the two groups was performed using an independent sample t-test. Continuous variables not conforming to normal distribution were represented by median (interquartile range) and compared between groups using the Mann-Whitney U test. Categorical variables were expressed as frequency (percentage), and comparisons were made using the chi-squared (χ 2) test or Fisher's exact test, as applicable. The correlation between serum calcium levels and patient outcomes was analyzed using univariate and multivariate Logistic regression. Results:The average age of the study subjects was (68.37±16.28) years, with 97 males (61.78%). The ages in the survival and death groups were (65.39±16.13) years and (76.80±13.67) years, respectively, with 66 males in the survival group and 31 in the death group. The history of malignancy (excluding multiple myeloma) was 37 cases and 23 cases, respectively, and serum albumin levels were (35.41±6.84) g/L and (30.82±5.75) g/L, respectively. Significant Statistical differences were observed in age, gender, history of malignancy (excluding multiple myeloma), and serum albumin were found between the survival and death groups (statistical values: t=4.04, χ 2=4.49, χ 2=7.51, t=3.85; all P<0.05). AIK 1 stage were 33.33%(21/63) and 64.15%(34/53), 2 stage were 36.51%(23/63) and 24.53%(13/34), 3 stage were 30.16%(23/63) and 11.32%(6/34) in the renal recovery and non-recovery groupsrespectively. Serum calcium at discharge in the renal recovery and non-recovery groups were (2.50±0.38) mmol/L and (2.70±0.58) mmol/L, respectively, with mean serum calcium levels of (2.60±0.29) mmol/L and (2.78±0.39) mmol/L, and lowest serum calcium levels of (2.28±0.36) mmol/L and (2.50±0.51) mmol/L, respectively. BNP levels were 118 (64, 283) ng/L and 248 (69, 1 383) ng/L, respectively. Significant differences in AKI stage, serum calcium at discharge, mean serum calcium, lowest serum calcium, and BNP were observed between the two groups (statistical values: χ 2=11.84, t=2.26, t=2.75, t=2.73, U=2.62, all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.062, 95% CI 1.027-1.098, P<0.001), history of malignancy (excluding multiple myeloma) ( OR=3.811, 95% CI 1.623-8.951, P=0.002), and serum albumin ( OR=0.889, 95% CI 0.829-0.953, P=0.001) were independent risk factors for in-hospital mortality of patients; severity of AKI(AKI2 OR=2.984, 95% CI 1.281-6.954, P=0.011, AKI3 OR=5.280, 95% CI 1.863-14.963, P=0.002) and serum calcium level at discharge ( OR=0.813, 95% CI 0.666-0.992, P=0.041) were independent risk factors affecting early renal recovery of patients. Conclusion:Serum calcium level is not associated with the risk of in-hospital mortality in patients with AKI accompanied by hypercalcemia but is related to the prognosis of early renal recovery. Proactively managing serum calcium, along with treatment of the primary malignancy and correction of hypoalbuminemia can help improve the prognosis of these patients.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.

Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.

Objective:To explore the efficacy and safety of eltrombopag in children with chronic primary immune thrombocytopenia (cITP).Methods:The clinical data of 13 children with cITP in Children′s Hospital of Soochow University from July 2017 to December 2021 were retrospectively analyzed.Results:Among 13 children with cITP, 7 males and 6 females, the median age was 5 years old, the median duration of illness was 2.2 years. The median therapy duration of eltrombopag was 5 months, the median maintenance dose was 25.0 mg/d, the median time to response was 4 weeks; complete response was in 5 cases, partial response was in 2 cases; 2 cases had skin disease, 1 case had arthralgia, 1 case had liver function abnormal, all complications did not cause serious impact.Conclusions:Eltrombopag was an effective and safe therapeutic option for children with cITP.

Objective:To evaluate the efficacy of the domestic D-Shant device for the treatment of patients with chronic heart failure (CHF) using echocardiography.Methods:Twenty-four CHF patients who were treated with domestic D-Shant device in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2020 to December 2021 were enrolled in the study. Pulmonary capillary wedge pressure (PCWP)/ left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure, interatrial septal gradient pressure, cardiac index and pulmonary/systemic blood flow ratio (Qp/Qs) were measured before and after implantation using right heart catheterization.Left atrial end-diastolic area index (LAEDAI), left atrial end-diastolic volume index (LAEDVI), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), right atrial end-diastolic diameter, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), right ventricular tractional area change (RVFAC), device shunt aperture, velocity and pressure, together with mitral and tricuspid regurgitation severity were measured using echocardiography before, and 1 month as well as 3 months after D-Shant device implantation. Clinical data were collected and analyzed including 6-minute walking test (6MWT), New York Heart Association (NYHA) classification and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation analysis was used to determine the relation between the changes in PCWP/LAP as well as echocardiographic parameters before and 3 months after implantation and NYHA classification. Binary Logistic regression analysis was performed to determine the predictive factors of NYHA classification improvement at 3-month follow-up after D-Shant device implantation.Results:①D-Shant devices were successfully implanted in all patients. ②Compared with preoperative values, invasive PCWP/LAP systolic, diastolic and mean pressures, transatrial septal gradient, and pulmonary systolic, diastolic and mean pressures decreased significantly after implantation(all P<0.001); Qp/Qs increased significantly after implantation( P<0.001). ③Compared with preoperative values, TAPSE, RVFAC and pulmonary artery flow velocity increased at 1 month after implantation(all P<0.05), whereas a significant reduction in mitral regurgitation grade, and an increase in LVEF and pulmonary artery flow velocity at 3 months after implantation(all P<0.05). Right atrial end-diastolic diameter, right ventricular end-diastolic diameter, LAEDAI, LAEDVI, LVEDVI, LVESVI, ratio of early to late diastolic peak velocities of mitral inflow(E/A), systolic peak velocity of mitral annulus at septal site(S′), ratio of early diastolic peak velocity of mitral inflow to diastolic peak velocity of mitral annulus(E/e′), pulmonary artery diameter, inferior vena cava diameter and degree of tricuspid regurgitation did not change among before, and 1 month as well as 3 months after implantation. There were no significant changes in the device shunt aperture, velocity and pressure between 1 month and 3 months after implantation(all P>0.05). ④The significant improvements in NYHA classification, KCCQ scores and 6MWT were observed at 1 and 3 months after implantation compared with preoperative values (all P<0.01). ⑤NYHA classification at 3 months after implantation was correlated with LVEF pre-post, PCWP/LAP pre-post, TAPSE pre-post and RVFAC pre-post ( rs=0.738, -0.730, 0.738, 0.723; all P<0.001). Logistic regression analysis showed that LVEF pre-post was an independent predictor for NYHA classification improvement at 3 months after implantation ( OR=0.687, 95% CI=0.475-0.992, P=0.045) . Conclusions:Domestic D-Shant device can effectively improve the cardiac function and clinical symptoms in patients with CHF. Echocardiography is a feasible and effective method to evaluate the benefits of domestic D-Shant device for the treatment of CHF.

Objective:To investigate the effect of preoperative pulmonary hypertension (PH) on right ventricular function in patients with heart transplantation(HTx) one year after surgery.Methods:A total of 120 patients who underwent HTx in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2017 to January 2020 were retrospectively recruited.According to the mean pulmonary arterial pressure (mPAP) obtained by preoperative right heart catheterization, the research subjects were divided into the pulmonary hypertension group (PH group, n=81) and without pulmonary hypertension group (NPH group, n=39). Conventional echocardiographic indices of right ventricular function such as right ventricular area change (RV-FAC), tricuspid annular plane systolic excursion (TAPSE), tricuspid lateral annular systolic velocity (S′), and two-dimensional speckle tracking imaging (2D-STI) strain parameters including right ventricular global longitudinal strain (RV-GLS), right ventricular free wall longitudinal strain (RV-FWLS) were obtained to assess the right ventricular function of grafted hearts. The echocardiographic parameters one year after the operation of the two groups were analyzed to compare the differences in right ventricular function and their correlation with preoperative mPAP. Results:The grafted heart RV-GLS and RV-FWLS were significantly decreased in the PH group (all P<0.01), while RV-FAC, TAPSE, and S′ were similar between the two groups (all P>0.05). RV-FWLS and RV-GLS correlated with preoperative hemodynamic parameter mPAP( rs=-0.46, -0.54; all P<0.05)while RV-FAC, TAPSE, and S′ were not significantly correlated with mPAP (all P>0.05). Conclusions:Preoperative PH correlates with right ventricular function in HTx patients 1 year after the operation. The absolute values of RV-FWLS and RV-GLS in HTx patients with preoperative PH decrease 1 year after the operation. 2D-STI is more sensitive than conventional echocardiography to monitor the changes in right ventricular function in HTx patients after the operation.

Objective : To investigate the predictive value of platelet volume distribution width ( PDW) , mean platelet volume (MPV) , and D ⁃dimer (D⁃D) on early shunt dysfunction in patients with decompensated cirrhosis treated with transjugular intrahepatic portosystemic shunt(TIPS) . Methods : A total of 28 patients with decompensated cirrhosis who developed shunt dysfunction within 6 months after TIPS were selected as the case group , and a 1 ∶ 2 matched control study was conducted. 56 patients matched by age ( ± 2) and gender who did not develop shunt dysfunction within 6 months after TIPS were selected as the control group. Spss23. 00 software was used to conduct univariate analysis to obtain statistically significant variables , and then conditional Logistic regression analysis was conducted with paired design , with P < 0. 05 being statistically significant. Results : Patients with a history of splenectomy , portal vein thrombosis , and those with poor liver function grade were more likely to have functional dysfunction after TIPS. Platelet count (PLT) , platelet volume distribution width (PDW) , mean platelet volume (MPV) , D ⁃dimer ( D⁃D) and Fibrinogen monomer ( FDPI) had statistically significant differences between the case group and the control group. The values of D ⁃D、PDW、MPV and FDPI in the case group were higher than those in the control group , while the value of PLT in the case group was lower than that in the control group. The OR values of PDW , MPV and D ⁃D were 2. 164 , 3. 826 and 1. 382 , respectively. ROC analysis results showed that the areas under PDW , MPV and D ⁃D curves were 0. 746 , 0. 773 and 0. 690 , respectively. Conclusion Compared with ultrasound , D ⁃D , PLT and PDW could predict shunt dysfunction earlier after TIPS. Patients with normal shunt function indicated by color Doppler ultrasonography in postoperative follow⁃up of TIPS should be closely observed for indicators such as D ⁃D , PLT and PDW , which is of important significance for clinical indication of shunt dysfunction in TIPS.

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

To investigate whether mammalian target of rapamycin (mTOR) signaling pathway is involved in peripheral nerve injury-induced hyperalgesia through activation of spinal dorsal astrocytes in rats.
 Methods: A total of 30 male Sprague-Dawley (SD) rats were randomly divided into 6 groups (n=5): the 1 day group (D1 group), the 4 days group (D4 group), the 7 days group (D7 group), the 14 days group (D14 group), the normal group and the sham group. The sciatic nerve chronic constriction injury (CCI) model was established in the D1, D4, D7 and D14 group. The normal group received no treatment while the sham group was only exposed the sciatic nerve. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured at the 1st, 4th, 7th, and 14th day after CCI in the different groups. Lumbar spinal cord were harvested on the 1st, 4th, 7th and 14th day in the D1, D4, D7, D14 group correspondingly, which were harvested on the 14th day in the normal group and the sham group. Distribution of mTOR in rat spinal cord was assessed by immunohistochemistry. The expressions of mTOR mRNA and protein in the spinal cord in different groups were determined by real-time PCR and Western blotting, respectively. Another 30 male intrathecal catheterized SD rats were randomly divided into 6 groups (n=5): a blank group, a CCI group, a CCI+early rapamycin (RAPA) group, a CCI+early dimethylsulfoxide (DMSO) group, a CCI+ later RAPA group, and a CCI+later DMSO group. The blank group didn't received any treatment; The CCI group was carried out the treatment of CCI model in the left hind limbs. 10 μL of 1% RAPA was given to the CCI+early RAPA group intrathecally at 4 hours after CCI for 3 days; the CCI+later RAPA group were treated with the same dose of RAPA on the 7th days after CCI for 3 days; the CCI+early DMSO group and the CCI+later DMSO group were injected with the same volume of 4% DMSO at the corresponding time as controls. The PWTL and PWMT were measured before and after intrathecal catheterization, and every other day after CCI. The lumbar spinal cords were selected and the expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn were examined by immunohistochemistry in the 14th day after CCI.
 Results: The immunohistochemistry positive particles of mTOR were widely distributed in the cytoplasm of the normal spinal neurons. Compared with the base line, the PWMT in the D14 group on the 1st, 4th, 7th and 14th day after CCI were significantly lower, and the PWTL on the 4th, 7th and 14th day after CCI were also significantly lower (P<0.05 or P<0.01). The expressions of mTOR mRNA and protein in the CCI groups (D1, D4, D7 and D14 group) were significantly increased than those in the normal group (P<0.05 or P<0.01). Compared with the CCI+early DMSO group, the PWMT and PWTL in the CCI+early RAPA group were obviously increased on 4th, 6th, 8th, 10th, 12th or 14th day after CCI (P<0.05 or P<0.01); compared with the CCI+later DMSO group, the PWMT and PWTL in the CCI+later RAPA group were also significantly increased at the 8th, 10th or 14th day after CCI (P<0.01 or P<0.05). The GFAP immunohistochemistry positive area and absorbance value in the dorsal horn of the lumbar spinal cord in the CCI rats were decreased in the CCI+early RAPA group compared with the CCI+early DMSO group (P<0.05 or P<0.01), and which were also decreased in the CCI+later RAPA group compared with the CCI+later DMSO group (P<0.05 or P<0.01).
 Conclusion: mTOR signaling pathway may be involved in hyperalgesia induced by peripheral nerve injury via spinal astrocyte activation in the dorsal horn of the spinal cord.
Animals ; Hyperalgesia ; Male ; Neuralgia ; Peripheral Nerve Injuries ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Spinal Cord ; TOR Serine-Threonine Kinases