Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

Objective:To investigate the preliminary efficacy of 3D printed individualized genioglossus advancement (GA) for the treatment of obstructive sleep apnea (OSA) in adults with micrognathia.Methods:The OSA patients with retropalatal and retroglossal collapses due to micrognathia underwent 3D printed individualized GA combined with Uvulopalatopharyngoplasty(UPPP) in Department of Otolaryngology, Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Clinical data including pre-and post-operative polysomnography (PSG), cephalometric measurements of genioglossus advancement, patient-reported symptom and surgical complications were collected. A comparison of pre-and post-operative data was conducted using paired t-tests. Results:Nineteen OSA patients with micrognathia successfully underwent 3D printed individualized GA combined with UPPP, and achieved an actual mean genioglossus advancement distance of (9.0±1.4) mm compared to the planned distance of (9.4±1.0) mm preoperatively ( t=0.81, P=0.427). Among the 14 patients followed up for more than 6 months, the mean AHI reduced by 60.4% at 6 months postoperatively, with 5 cases (5/14) cured and 5 cases (5/14) showing significant improvement, resulting in an overall surgical response rate of 10/14. All patients expressed satisfaction with their postoperative facial appearance, with 13 cases perceiving an improvement in attractiveness. Two patients reported temporary genial numbness, and one patient experienced temporary mandibular occlusal asthenia. Conclusion:The 3D printed individualized GA combined with UPPP effectively reduces AHI in adult OSA patients with micrognathia, accompanied by a low incidence of surgical complications and high patient satisfaction regarding postoperative facial appearance.

Objective:To analyze the patterns of dynamic functional connectivity(dFC) at rest in different obsessive-compulsive disorder(OCD) subtypes based on gray matter volume, and explore the relationship between abnormal gray matter volume and dFC patterns and clinical symptoms in different OCD subtypes.Methods:Clinical data were prospectively collected from a total of 48 patients with OCD from inpatient and outpatient departments of the Fourth Affiliated Hospital of Qiqihar Medical College(20 cases) and Qiqihar Mental Health Center(28 cases) from September 2013 to March 2020. There were 33 males and 15 females, aged 18 to 42(27.1±6.7) years. During the same period, 39 age-matched healthy controls were also recruited, including 31 males and 8 females, aged 18 to 43(28.5±8.6) years. Structural and resting-state functional magnetic resonance imaging scans were performed on 48 OCD patients(OCD group) who met the ICD-10 diagnostic criteria and 39 healthy controls(control group). Using voxel-based morphometry(VBM) and semi-supervised machine learning methods, the patient group was characterized by gray matter volume to perform subtype analysis, and brain regions with abnormal gray matter volume were selected as regions of interest for whole-brain voxel-wise dFC analysis. Correlations between abnormal gray matter volume and dFC and clinical symptoms in OCD patients were analyzed.Results:Based on gray matter volume, OCD patients were computed into two subtypes, of which subtype 1 increased gray matter volume in the right central posterior gyrus(809 voxels; t=4.31; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed), and subtype 2 showed reduced gray matter volume in the left superior temporal gyrus(1 118 voxels; t=-4.37; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, the dFC between the right central posterior gyrus and left medial superior frontal gyrus was significantly reduced(187 voxels; t=-4.42; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed); in subtype 2, dFC between the left superior temporal gyrus and left hippocampus, and left central opercular cortex was significantly reduced(272 voxels、99 voxels; t=-4.69, -5.01; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, dFC between the right central posterior gyrus and left medial superior frontal gyrus was negatively correlated with illness duration( r=-0.579; P=0.002, uncorrected). In subtype 2, dFC between the left superior temporal gyrus and left hippocampus was positively correlated with illness duration( r=0.578; P=0.003, uncorrected). Conclusions:In the resting state, patients with different subtypes of OCD may have different patterns of dFC abnormalities based on gray matter volume.

Objective:To analyze the patterns of dynamic functional connectivity(dFC) at rest in different obsessive-compulsive disorder(OCD) subtypes based on gray matter volume, and explore the relationship between abnormal gray matter volume and dFC patterns and clinical symptoms in different OCD subtypes.Methods:Clinical data were prospectively collected from a total of 48 patients with OCD from inpatient and outpatient departments of the Fourth Affiliated Hospital of Qiqihar Medical College(20 cases) and Qiqihar Mental Health Center(28 cases) from September 2013 to March 2020. There were 33 males and 15 females, aged 18 to 42(27.1±6.7) years. During the same period, 39 age-matched healthy controls were also recruited, including 31 males and 8 females, aged 18 to 43(28.5±8.6) years. Structural and resting-state functional magnetic resonance imaging scans were performed on 48 OCD patients(OCD group) who met the ICD-10 diagnostic criteria and 39 healthy controls(control group). Using voxel-based morphometry(VBM) and semi-supervised machine learning methods, the patient group was characterized by gray matter volume to perform subtype analysis, and brain regions with abnormal gray matter volume were selected as regions of interest for whole-brain voxel-wise dFC analysis. Correlations between abnormal gray matter volume and dFC and clinical symptoms in OCD patients were analyzed.Results:Based on gray matter volume, OCD patients were computed into two subtypes, of which subtype 1 increased gray matter volume in the right central posterior gyrus(809 voxels; t=4.31; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed), and subtype 2 showed reduced gray matter volume in the left superior temporal gyrus(1 118 voxels; t=-4.37; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, the dFC between the right central posterior gyrus and left medial superior frontal gyrus was significantly reduced(187 voxels; t=-4.42; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed); in subtype 2, dFC between the left superior temporal gyrus and left hippocampus, and left central opercular cortex was significantly reduced(272 voxels、99 voxels; t=-4.69, -5.01; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, dFC between the right central posterior gyrus and left medial superior frontal gyrus was negatively correlated with illness duration( r=-0.579; P=0.002, uncorrected). In subtype 2, dFC between the left superior temporal gyrus and left hippocampus was positively correlated with illness duration( r=0.578; P=0.003, uncorrected). Conclusions:In the resting state, patients with different subtypes of OCD may have different patterns of dFC abnormalities based on gray matter volume.

The initiation and operation of the tissue repair program between the broken ends after fracture is very important for fracture healing, which goes through three intertwined and gradual evolution stages: hematoma inflammatory organization stage, primitive callus formation stage and callus remodeling stage. It is completed by a variety of tissues, cells and cytokines in the bone marrow cavity. In the study of the mechanism of fracture healing, it is found that there are many signal pathways and molecules regulating bone repair, including bone formation, bone remodeling and neovascularization. At the cellular level, it regulates osteoblasts, chondrocytes, osteoclasts and endothelial cells. Hippo signaling pathway is a signal pathway that maintains the size of organs and the balance between cell proliferation and apoptosis, and also plays an important role in maintaining bone homeostasis and bone metabolism. In the process of regulating bone development and repair, it regulates the physiological activities of cells in microenvironment through protein kinase cascade reaction and transcriptional coactivator. The upstream and downstream effectors of Hippo signal pathway directly or indirectly regulate the proliferation, differentiation and apoptosis of bone metabolic cells, and the interaction with Wnt signal pathway, Notch signal pathway and other important pathways related to bone repair show that Hippo signal pathway plays an important role in the regulation of fracture healing and may become a new target to promote fracture healing. This article reviews the regulatory mechanism of Hippo signaling pathway and its regulatory role in the process of fracture healing, and looks forward to the research prospect of promoting bone healing by using it as a target.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

BACKGROUND: There are many studies on the effect of different experimental parameters on the tetragonal phase of zirconia, but it is unclear whether pH values have effects on the tetragonal phase in hydrothermal reactionOBJECTIVE: To prepare two zirconia systems via hydrothermal method and to regulate the tetragonal phase purity and control the grain size of zirconia (ZrO2) crystal by pH values.METHODS: Analytical reagents Zr(NO3)4?5H2O and Y(NO3)3?6H2O were adopted as reactors, and nano-sized neat ZrO2 and yttria-stabilized tetragonal ZrO2 polycrystal (Y-TZP) powders were synthesized using the hydrothermal method. X-ray diffraction was adopted to characterize the influence of pH values and pH regulators (NaOH solution and ammonium hydroxide/NaOH solution) on phase purity and grain size of tetragonal zirconia.RESULTS AND CONCLUSION: Pure zirconia samples with a grain size lower than 20 nm were obtained through the hydrothermal method, and samples with higher tetragonal phase content compared to monoclinic phase could be derived when the pH value was higher than 10. The optimal pH values for neat zirconia and Y-TZP were 13 and 12,respectively. Furthermore, the ammonium hydroxide/NaOH solution was more favorable to enhance the content of tetragonal zircona. Therefore, the control of pH values and rational choice of pH regulators can improve the tetragonal phase purity and grain size of zirconia.

Objective To explore the demographic factors and the risk of the pedicle screw insertion of the narrow pedi?cles. Methods Thoracolumbar spine thin?section CT image data of 312 adults from September 2014 to September 2015 were ana?lyzed. The pedicle width,medial and lateral cortical thickness, spongy bone thickness, spongy bone thickness/cortical thickness, e angle and screw path length of each pedicle were measured. The incidence and the distribution characteristics of the narrow pedi?cle were analyzed. Anatomic parameters and age, gender and stature were compared between the narrow pedicle group and non?narrow pedicle. The risk of the pedicle screw insertion of the narrow pedicle was assessed. Results Among the 3 081 pedicles, 74 narrow pedicles were determined as their pedicles width were less than 5 mm, and the proportion of narrow pedicle was 2.40%. Among the 312 subjects, 26 subjects were found having narrow pedicles, and the proportion of individuals with narrow pedicles in the population was 8.33% (26/312). The incidences of narrow pedicle in thoracolumbar spine were T10 0.32%, T11 0.32%, T12 0.98%, L1 7.54%, L2 2.92%. The spongy bone thickness, spongy bone thickness/cortical thickness of narrow pedicle were lower than non?narrow pedicle. However, there were no significant differences of medial and lateral cortical thickness, e angle and screw path length between the narrow pedicle and non?narrow pedicle. Difference of the mean age between the two subjects groups had no statistical significance. The percentage of female in narrow pedicle subjects group was 84.6%(22/26), which was higher than that in non?narrow pedicle subjects group (49.7%, 142/286). The mean stature of the male and female of stenosis pedicle group subjects were 163.8±1.3 cm and 152.5±4.3 cm, which were shorter than those of non?narrow subjects pedicle group (169.5±5.6 cm, 160.1±6.6 cm). The percentage of the cortical bone breakthrough by the pedicle screws of narrow pedicle group was (84.6%, 27/32), which was higher than that of non?narrow pedicle group (14.7%, 33/224). Conclusion L1 is the most common segment of thoracolumbar spine that narrow pedicle exist, which is the result of reduction of the spongy bone thickness. Narrow pedicle mostly appears in short stature female. There is high risk of cortical bone breakthrough by insertion of the posterior pedicle screws in the narrow pedicle.

Objective To evaluate the clinical outcome of bleeding control by preoperative embolization of internal iliac artery with DSA and intra?operative presetting abdominal aorta balloon, combine with the operation techniques of exposure, reduc?tion and internal fixation of pelvic fracture through lateral?rectus approach. Methods From March 2012 to May 2015, 7 patients with type C3 pelvic fractures admitted to our department from March 2012 to May 2015, treated with preoperative embolization of internal iliac artery under digital subtraction angiography 2 h before surgery and presetting abdominal aorta balloon were retrospec?tively reviewed. There were 3 males and 4 females, with an average age of 34 years (range, 16 to 61 years). According to AO classi?fication, all 7 cases belonged to type C3 (3.2:5 cases;C3.3:2 cases), including 5 cases with limb fracture, 2 cases with craniocere?bral trauma, 4 cases with pulmonary contusion, 2 cases with injury of abdominsal organs. Time from injury to operation was 19 days on average (10 to 33 days). Patients received damage control surgery treatment including bleeding control and temporary ex?ternal fixation, and ipsilateral tractions with heavy weight, intensive care and corrections of general situation before operation. The fracture model was manufactured by 3D printing and fracture reduction was simulated on computer preoperatively. Embolization of internal iliac artery was performed in the side of severe displaced sacroiliac joint with DSA 2 hours preoperatively. Reduction was performed to stabilize anterior-posterior pelvic ring and acetabular fractures via the intraoperative lateral?rectus approach. And 2 cases were performed by temporary balloon occlusion of abdominal aorta (≤60 min) for bleeding control in reduction of in the side of sacroiliac joint fractures. Results All the 7 cases had undergone the operations successfully, and the operating time was from 135-320 min with blood loss from 440-3 350 ml. According to Matta radiological evaluation postoperatively, reduction of pelvic fracture was rated as anatomic in 5 cases, satisfactory in 2, without complications. All 7 cases were complicated with lumbosacral plexus injury or lumbosacral trunk injury at different degrees (M0 2 cases, M1 2 cases, M2 2 cases, M3 1 case). According to the BMRC scoring system, 5 cases had well recovered and the other 2 cases had no improvement after three months (M4 2 cases, M5 3 cases). Conclusion Surgical management of pelvic fracture through preoperative internal iliac artery embolization and intra?oper?ative occlusion of abdominal aorta could effective control bleeding and achieve favorable conditions for reduction. Lateral?rectus approach can provide adequate exposure of the anterior and posterior ring, and this approach could also provide excellent visual control of reduction and fixation.