Objective To investigate the correlation of sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2a(SERCA2a)and blood urea nitrogen(BUN)to albumin(ALB)ratio(BAR)with cardiac function and prognosis in patients with chronic heart failure(CHF).Methods A total of 200 CHF patients admitted to this hospital from January 2021 to January 2023 were selected as the CHF group and 100 healthy people un-dergoing physical examination as the control group.CHF patients were divided into class Ⅰ group(38 cases),class Ⅱ group(40 cases),class Ⅲ group(54 cases)and class Ⅳ group(68 cases)according to the New York Heart Association(NYHA)cardiac function classification after admission.According to the prognosis,they were divided into poor prognosis group(60 cases)and good prognosis group(140 cases).Serum SERCA2a BUN,ALB levels were measured and BAR was calculated.Spearman rank correlation coefficient was used to analyze the correlation between serum SERCA2a,BAR and NYHA cardiac function classification in CHF pa-tients.Taking the prognosis of CHF patients as the dependent variable,a multivariate unconditional Logistic regression model was established to determine its influencing factors.Receiver operating characteristic curve was drawn to evaluate the predictive value of serum SERCA2a and BAR for poor prognosis of CHF patients.Results Compared with the control group,the serum SERCA2a level was decreased and BAR was increased in the CHF group(P＜0.05).The level of SERCA2a in class Ⅰ group,class Ⅱ group,class Ⅲ group and classⅣ group decreased and BAR increased successively(P＜0.05).The NYHA classification was negatively cor-related with serum SERCA2a level(rs=-0.756,P＜0.05),and positively correlated with BAR(rs=0.722,P＜0.05).After 1-year follow-up,the incidence of poor prognosis in 200 CHF patients was 30.00％(60/200).Increased NYHA class(OR=1.936,95％CI:1.115-3.364),atrial fibrillation(OR=3.269,95％CI:1.078-9.913),N-terminal pro-B-type natriuretic peptide(OR=1.002,95％CI:1.001-1.009)and BAR(OR=1.169,95％CI:1.082-1.263)were independent risk factors for poor prognosis in patients with CHF(P＜0.05),increased left ventricular ejection fraction(OR=0.810,95％CI:0.716-0.916)and SERCA2a(OR=0.964,95％CI:0.947-0.981)were independent protective factors(P＜0.05).The area under the curve of serum SERCA2a combined with BAR to predict the poor prognosis of CHF patients was 0.865(95％CI:0.810-0.910),which was larger than 0.784(95％CI:0.720-0.839)and 0.777(95％CI:0.713-0.833)predicted by serum SERCA2a and BAR levels alone,and the difference was statistically significant(Z=2.944,3.250,P＜0.05).Conclusion The decrease of SERCA2a and the increase of BAR are closely re-lated to cardiac function and prognosis in patients with CHF.Serum SERCA2a combined with BAR has a higher value in predicting poor prognosis in patients with CHF.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To investigate the effect of a degradable high-purity magnesium screw in fixing the greater trochanter bone flap of a lateral circumflex femoral artery transverse branch in the treatment of ischemic necrosis of femoral head in young and middle-aged adults.Methods:From February 2017 to February 2019, 12 cases (15 hips) of young and middle-aged patients with avascular necrosis of femoral head were treated in the Department of Orthopaedic of Affiliated Zhongshan Hospital of Dalian University. The age of patients was 30-53 years old. According to Association Research Circulation Osseous (ARCO), 2 hips were graded in stage II b, 4 in ARCO II c, 1 in ARCO III a, 5 in ARCO III b, 2 in ARCO III c and 1 in ARCO IV. The greater trochanter bone flap with a lateral circumferential vascular branch was used to fill the necrotic area, and fixed by a biodegradable high purity magnesium screw in the bone flap transfer. At 3, 6 and 12 months postoperation, the patient came to the hospital outpatient clinic for follow-up, and then were reviewed once a year. Imaging efficacy was evaluated by comparing preoperative and postoperative imaging. The Harris score and Visual Anoalogue Scale (VAS) score were tested at 12 and 24 months after surgery. The Harris score and VAS score before and after surgery were compared by Friedman test, and P<0.05 was considered statistically significant. Results:All 12 patients (15 hips) were entered in the 24-36 months of follow-up. At 12 and 24 months after surgery, Harris score was found at 87 (86, 92) and 90 (87, 92) respertively, which were both higher than that before surgery [59 (52, 74)] with a significant statistical difference ( Z=-3.743, Z=-4.473, P<0.05). However, there was no significant difference in Harris scores between 12 and 24 months after the surgery ( Z=-0.730, P>0.05). At the 12 and 24 months after surgery, VAS score was found at 3 (2, 3) and 2 (1, 3) respertively, which were both lower than that before surgery [6 (5, 6) ] with a significant statistical difference ( Z=-3.560, Z=-4.656, P<0.05). There was no statistical difference in VAS scores between 12 and 24 months after surgery ( Z=-1.095, P>0.05). X-ray and CT scan showed that the bone flaps healed well and the areas of osteonecrosis were repaired. Thirteen femoral heads were in good shape, and 2 femoral heads had further collapse of hips. No patients underwent joint replacement surgery at the time of last follow-up. Conclusion:Fixation of the greater trochanter flap of lateral circumflex femoral artery transverse branch with a degradable high-purity magnesium screw can ensure the healing of the flap at the implantation site and avoid the displacement and shedding of the flap. It is a new therapeutic option to treat the avascular necrosis of femoral head of young and middle-aged people.

Objective:To dynamically trace the migration and therapeutic effects of human bone marrow mesenchymal stem cells (MSCs) in mice with liver injury after cell transplantation through in vivo bioluminescent imaging (BLI).Methods:The MSCs were transfected with the lentivirus CMV-Luciferase2-mKate2 and mKate2 positive cells were purified and screened by fluorescence-activated cell sorting (FACS) after 96 h. The purified MSCs-R (MSCs-CMV-Luciferase2-mKate2) were used by in vitro and in vivo BLI. The mice (male BALB/c nude mice) were divided into 4 groups with 9 mice per group by random number table method, including (1) Liver injury experimental group: The liver injury model was established by intraperitoneal injection of CCl 4, and MSCS-R transplantation through spleen injection was performed 24 h later; (2) Control experimental group: The same volume of phosphate buffer (PBS) was injected intraperitoneally, and MSCS-R transplantation through spleen injection was performed 24 h later; (3) Liver injury group: Liver injury model was established and PBS was injected into the spleen;(4) Blank group: The mice were intraperitoneally injected of PBS.BLI was performed daily after cell transplantation until light signals disappeared in the liver region, and the pathological examination of liver tissue was obtained 14 d after MSCs-R transplantation. Linear regression analyses were performed to determine the correlation between the optical signal intensity and the number of cells, and statistical differences of the optical signal intensity between liver injury experimental group and control experimental group were evaluated using the Student′s t test. Results:The MSCs were readily transfected with lentivirus CMV-Luciferase2-mKate2 for 96 h. The transfected MSCs were purified by FACS and more than 95% of MSCs were mKate2 positive. The optical signal intensity of MSCs-R detected by BLI in vitro significantly correlated with cell numbers in vitro (R 2=0.980). In both of liver injury experimental group and control experimental group, cell migration to the liver was observed on the first day after intrasplenic transplantation of MSCs-R, and the optical signal intensity in the area of liver of liver injury experimental group was higher than that of control experimental group ( t=15.476, P<0.001). The optical signal intensity in the hepatic area was observed in 11 d after transplantation in liver injury experimental group, compared to control experimental group in 5 d. Optical signal was not detected in mice in the other two groups. Histopathology showed that the degree of liver injury after MSCs-R transplantation was significantly lower in liver injury experimental group than control experimental group. Conclusions:The dynamical migration of MSCs transplanted to the spleen and settled in the damaged liver could be tracked by BLI, and liver injury can prompt MSCs directionally migrate to the damaged tissues and play their role in repairing liver injury.

Inguinal incarcerated hernia in adults is a common acute abdomen in hernia and abdominal wall surgery. If not treated in time, it is easy to progress to constrictive hernia, lead to intestinal ischemic necrosis, cellulitis of tegmental tissue outside the hernia, hernia sac empyema, intestinal fistula, and even cause toxic shock, with significantly increased mortality. The types of incarceration are different and the corresponding management methods are different. Based on the proposal of the concept of musculopubic foramen hernia repair, inguinal incarcerated hernia includes incarcerated indirect hernia, incarcerated direct hernia, incarcerated femoral hernia, etc. At present, there is no uniform standard for the comprehensive treatment of different types of inguinal incarcerated hernia, and the clinical management strategies of adult inguinal incarcerated hernia still face serious challenges.

Background and Objectives: Tracking of the tumor progression by MSCs-based therapy is being increasingly important in evaluating relative therapy effectively. Herein, Bioluminescence imaging (BLI) technology was used to dynamically and quantitatively track the hepatocellular carcinoma suppressive effects by human umbilical cord mesenchymal stem cells (UC-MSCs). Methods: and Results: The stem cells present typical phenotypic characteristics and differentiation ability by morphology and flow cytometry analysis of marker expression. Then, the growth inhibition effect of conditioned medium and UC-MSC on H7402 cells was studied. It is found both the conditioned medium and UC-MSC can effectively decrease the proliferation of H7402 cells compared with the control group. Meanwhile, the relative migration of UC-MSC to H7402 is also increased through the transwell migration assay. In addition, a mice hepatoma tumor model was built by H7402 cells which can express a pLenti-6.3/DEST-CMV-luciferase 2-mKate2 gene. The effect of stem cells on growth inhibition of tumor in a mice transplantation model was dynamically monitored by bioluminescence imaging within 5 weeks. It has shown the bioluminescence signal intensity of the tumor model was significantly higher than that of the UC-MSC co-acting tumor model, indicating that the inhibition of UC-MSC on liver cancer resulted in low expression of bioluminescent signals. Conclusions The microenvironment of UC-MSCs can effectively inhibit the growth of liver cancer cells, and this therapeutic effect can be dynamically and quantitatively monitored in vivo by BLI. This is of great significance for the imaging research and application of stem cells in anticancer therapy.

Objective To summarize the experience of surgical treatment of severe ventricular septal defect (VSD) accompanied by pulmonary hypertension (PH) in little infants. Methods The clinical data of 11 patients with VSD accompanied by PH admitted to the Department of Cardiac Surgery of Tianjin Children's Hospital of the Pediatric Clinical College in Tianjin Medical University from January 2016 to January 2017 were retrospectively analyzed. There were 6 males and 5 females, with the ages of 3 - 6 months, mean (5.36±1.03) months and body weights 4.2 - 7.5 kg, mean (5.9±1.0) kg. Preoperatively, all patients had recurrent pneumonia and heart failure history. After 2 - 3 times of medical treatment in hospitals, the patients underwent sub-acute radical operation under cardiopulmonary bypass. All patients were followed-up with echocardiography, chest X-ray and electrocardiogram examinations at 3, 6 and 12 months after heart surgery. Results After operation, all the children spontaneously recovered the heart beats, the stay times in surgical intensive care unit (SICU) were 2 - 7 days, and total hospitalization times were 12 - 17 days. All patients were followed up for 12 months, no death occurred in the whole group, and the heart and lung functions recovered satisfactorily. Conclusions Little infants with large VSD and PH should undertake operation as early as possible. The patients with recurrent pneumonia, heart failure in a short term should receive medical and surgical doctors' cooperative treatment, and the disease situation ought to be adjusted with one's best ability to a stable status when the sub-acute surgery can be carried out safely.

Objective To investigate the effects of melatonin on the proliferation of neural stem cells (NSCs) in cerebral ischemia reperfusion (IR) rats, and to explore the possible mechanisms. Methods Seventy-two rats were randomly divided into the normal control group (n=12), model group (n=30) and melatonin group (n=30) according to the random number table. The rats in the model group and melatonin group were divided into four subgroups: 6 h, 24 h, 72 h and 7 d subgroups according to the time after IR. The morphological changes of the subventricular zone (SVZ) were examined by HE staining;the effects of melatonin on NSCs proliferation were examined by immunofluorescence staining;the effects of melatonin on toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB p65 protein were examined by immunohistochemistry staining and Western blotting analysis. The correlation between the proliferating NSCs and TLR4 protein or the NF-κB p65 protein was analyzed by linear regression analysis. Results HE staining showed that the cells in the SVZ of rats in the model group were in disorder and irregular in shape. In the melatonin group, the cells in the SVZ of the injured side were relatively well arranged. Immunofluorescence staining showed that the number of proliferating cell nuclear antigen (PCNA)+Nestin+4',6-diamidino-2-phenylindole (DAPI)+cells in the SVZ of the model (498.47 ± 26.44/mm2) and melatonin groups (623.10 ± 39.70/mm2) increased gradually, and reached a higher level after IR for 7 days, which were significantly higher than the normal control group (203.91 ± 32.23/mm2) (F=35.193, 170.344, 277.536, 285.947, all P＜0.01). The number of PCNA+Nestin+DAPI+cells in the melatonin group rats at each time points was significantly higher than that in the model group (F=102.561, 91.244, 168.502, 38.013, all P＜0.01). Immunohistochemistry staining showed that the numbers of TLR4+and NF-κB p65+cells in the SVZ of the model (740.02±31.63/mm2;710.01± 26.59/mm2) and melatonin groups (555.57 ± 25.28/mm2;528.85 ± 30.60/mm2) increased gradually, and reached a higher level 7 d after IR, which were significantly higher than the normal control group (107.97±12.84/mm2;109.80±13.89/mm2) (F=21.413, 263.059, 873.691, 1 037.098, all P＜0.01;F=26.374, 372.940, 854.826, 929.018, all P＜0.01). There were less TLR4+(F=7.641, 25.135, 66.094, 103.753, all P＜0.05) and NF-κB p65+cells (F=18.612, 69.597, 113.113, 119.814, all P＜0.01) in the melatonin group as compared with those in the model group at each time points. Western blotting analysis showed that the expression of TLR4 (0.87±0.08;0.68±0.06) and NF-κB p65 (0.72±0.05;0.58±0.05) protein was higher in the model and melatonin groups as compared with the normal control group (0.35±0.04, 0.31±0.03;F=107.43, F=132.51, both P＜0.01). The expression of the TLR4 and NF-κB p65 protein was lower in the melatonin group as compared with that in the model group (P＜0.01). Linear regression analysis showed that the differences of PCNA+Nestin+DAPI+cells were all negatively correlated with that of the TLR4+cells and NF-κB p65+cells in the melatonin group (r2=0.838, r2=0.813, both P＜0.01). Conclusion Melatonin can inhibit the expression of TLR4 and NF-κB p65 protein, thus promote the proliferation of endogenous NSCs in cerebral ischemia reperfusion rats.

Objective To investigate the diagnostic value of urinary neutrophil gelatin enzyme-related lipid delivery protein (NGAL) and kidney injury molecule-1 (KIM-1) in the acute kidney injury (AKI) after cardiopulmonary bypass (CPB) operation in children with non-cyanotic congenital heart disease (CHD). Methods A retrospective analysis was conducted. 200 CPB undergoing cardiac surgery in children with non-cyanotic CHD admitted to Tianjin Children's Hospital from June 2015 to May 2017 were enrolled. All patients were divided into AKI group and non-AKI group within 48 hours after operation, and the two groups matched with age, sex, weight, basic complications, operation time and other factors. The differences in serum creatinine (SCr), urinary NGAL and KIM-1 [corrected for urinary creatinine (UCr)] between the two groups before and after operation were compared. The early diagnosis value of urinary NGAL and KIM-1 on AKI was analyzed by the receiver operating characteristic curve (ROC). Results There were 32 patients with different degrees of AKI 48 hours post operation, and the incidence was 16.0%; 60 cases were enrolled in non-AKI group. Compared with non-AKI group, urinary NGAL at 2 hours after operation, urine KIM-1 at 4 hours after operation, and SCr at 10 hours after operation in AKI group were significantly increased, which decreased gradually after reaching peak at 6, 8, 24 hours respectively. It was shown by ROC curve analysis that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of postoperative 2-hour urine NGAL, 4-hour urine KIM-1 and 10-hour SCr for diagnosis of AKI were 0.940 (95%CI = 0.890-0.990), 0.939 (95%CI = 0.891-0.986) and 0.959 (95%CI = 0.916-1.000) respectively. When the cut-off value of postoperative 2-hour urine NGAL was 588.0 μg/g, the sensitivity was 87.5%, the specificity was 95.0%, the accuracy was 93.5%; when the cut-off value of postoperative 4-hour urine KIM-1 was 9.55 ng/mg, the sensitivity was 87.5%, the specificity was 91.7%, the accuracy was 90.2%; and when the cut-off value of postoperative 10-hour SCr was 61.90 μmol/L, the sensitivity was 90.6%, the specificity was 95.0%, and the accuracy was 95.7%. Conclusion Urine NGAL and KIM-1 can be used as biomarkers for early diagnosis of AKI after CPB for the non-cyanotic CHD in children.

Objective To compare the biomechanical characteristics of lengthened sacroiliac screw and long sacroiliac screw fixated in different ways for the treatment of central vertical sacral fractures to provide reference for clinical practice.Methods A finite element model with three dimensions of Tile type C pelvic ring injury (central type Denis Ⅲ fracture of sacrum) was produced.The central sacral fractures were fixated with lengthened sacroiliac screw or long sacroiliac screw in 7 types of models respectively as follows.(1) One long sacroiliac screw was fixated in S1 segment from the right (C1);(2) One long sacroiliac screw was fixated in S2 segment from the right (C2);(3)Two long sacroiliac screws were fixated in S1 and S2 segments respectively from the right (C12);(4) One long sacroiliac screw was fixated in S1 segment from the right and one long sacroiliac screw was fixated in S2 segment from the left (C12hybrid);(5) One lengthened sacroiliac screw was fixated in S1 segment from the right (J1);(6) One lengthened sacroiliac screw was fixated in S2 segment from the right (J2);(7)Two lengthened sacroiliac screws were fixated in S1 and S2 segments respectively from the right (J12).The shift and angle displacement of the central superior surface of sacrum in the case of standing on both feet were measured and compared.The maximum Von Mises stresses in different positions were measured.And various mechanical indices (including stresses of various parts and stress distribution of screws and pelvis,etc) were also quantified and compared.Results The stability of the posterior ring-screw complex was optimal when the sacrum was fixated with S1 & S2 lengthened sacroiliac screws.The maximum Von Mises stresses of screw were affected by sacral segments,namely,S1 ＞ S2 ＞ S1& S2.The maximum Von Mises stress of screws in S1 and S2 segments were similar.The maximum stress of the lengthened sacroiliac screw was lower than that of the long sacroiliac screw.The maximum Von Mises stress of bilateral sacroiliac joints in the lengthened sacroiliac screw fixation model was similar to that of normal pelvis.The maximum stress in the left sacroiliac joint of the long sacroiliac screw fixation model was larger than that of the normal pelvis.The maximum Von Mises stress of screw-bone interface of the long sacroiliac screw fixation model was larger than that of the lengthened sacroiliac screw fixation model.The screw stress distribution of the lengthened sacroiliac screw was superior to that of the long sacroiliac screw,and the screw stress distribution of the double segment fixation was superior to that of the single segment fixation.There was relatively less difference between the pelvic stress distribution of double segment fixation model and that of the normal pelvic model.Conclusion The fixation of S1 & S2 lengthened sacroiliac screws utilized in central sacral fractures of Tile C pelvic ring injury results in a more stable posterior pelvic ringscrew complex,more dispersed screw stress and better pelvic stress distribution which is closed to normal,and can also reduce the risk of internal fixation failure as well as lower back pain.