Superb microvascular imaging(SMI)is a new kind of Doppler technology,being sensitive for displaying low-velocity microvascular blood flow in muscles,tendons,synovium,nerves and reflecting microcirculation changes,able to provide imaging evidences for diagnosing musculoskeletal system diseases,monitoring processes and evaluating therapeutic effect.The research progresses of SMI applicated in musculoskeletal diseases were reviewed in this article.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective To observe the impact of ultrasonic image quality on the consistency of artificial intelligence(Al)assisted diagnosis system and manual measurements of biological indicators of developmental dysplasia of hip(DDH).Methods Hip ultrasonic data of 75 DDH and 345 non-DDH children were retrospectively analyzed,and the quality of ultrasonic images were subjectively scored.An evaluation model of ultrasonic image quality was constructed based on 140 ultrasonic images acquired from 140 cases(group A,containing 25 DDH and 115 non-DDH)using entropy weighting method,the weight of anatomic structures and impact factors related to DDH were obtained.The comprehensive image quality scores of other ultrasonic images acquired from 280 cases(group B,including 50 DDH and 230 non-DDH)were calculated,and the images in group B were classified into grade A,B and C in descending order.The consistency of AI and manual measurements of DDH biological indicators in group B was assessed.Results The weight of each anatomic structure and impact factors of DDH obtained with the model were as follows:The lower edge of iliac branch＞ilium＞glenoid labrum＞bony margin＞femoral head＞motion artifacts.In group B,grade A was observed in 67(9 DDH and 58 non-DDH),grade B was found in 160(26 DDH and 134 non-DDH),while grade C was noticed in 53(15 DDH and 38 non DDH)images.Except for β,femoral head coverage(FHC)and femoral head length diameter,the consistencies between AI and manual measurements of other indicators of DDH were grade A＞B＞C.In group B,AI and manual measurements were more consistent in DDH than in non-DDH cases.Conclusion Ultrasonic image quality affected the consistency between AI and manual measurements of biological indicators of DDH.When image quality was not good enough,further attention should be paid to measurement of FHC and sizes of femoral head.

To report 7 Chinese children with characteristic hyperpigmented macules on the forehead and temples. Among the 7 cases, there were 2 males and 5 females, with the age at onset ranging from 9 to 24 months (12.43 ± 5.32 months), and the disease duration being 1 - 4 months (2.57 ± 1.27 months). Skin examination revealed that the children presented with varying numbers of irregular brown macules and patches scattered on their foreheads and temples, without obvious desquamation. Dermoscopic examination revealed multiple yellowish-brown patches with irregular borders, and linear vessels were observable in some skin lesions. A diagnosis of acquired facial hyperpigmented macules was made in these children. The children received no treatment. After 2 years of follow-up, hyperpigmented macules completely subsided in 2 cases and regressed to varying degrees in 4 cases, while 1 case exhibited no changes in the skin lesions. Considering the literature and the cases discussed in this article, it is hypothesized that acquired facial hyperpigmented macules in young children may represent an independent condition.

Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.

Objective:To evaluate the effects of split-filter dual-energy CT (SF-DECT) in improving image quality at low doses in the process of abdominal examinations for children.Methods:A preliminary study was conducted using child phantoms. Furthermore, 20 children aged 4-6 years were recruited prospectively for clinical validation from June 2020 to December 2020. Conventional single-energy CT (SECT) and SF-DECT were employed to scan the abdominal areas of the phantoms and children. Then, the CT values, image noise, contrast to noise ratios (CNRs), and image subjective scores of SF-DECT and SECT were compared under various doses (1, 2, 3, and 4 mGy).Results:For the phantoms under doses of 3 and 4 mGy, SF-DECT decreased the image noise by 18.9% and 23.6%, respectively, and increased the liver and kidney CNRs (CNR liv and CNR kid) by 12.8% and 31.9% at most, respectively, compared to SECT ( Z = 3.00, 5.17, P < 0.001). For children, SF-DECT decreased image noise ( Z = 4.64, P < 0.001) and increased CNR liv and CNR kid ( Z = 3.78, 3.39, P < 0.001). For both the phantoms and the children, the subjective scores of images scanned using the SF-DECT were higher than those scanned using the SECT ( Z = 1.96-3.80, P < 0.05). Conclusions:Compared with SECT, SF-DECT can improve the quality of children′s abdominal images. This technique has a certain prospect of optimizing abdominal CT for children. However, it is necessary to conduct in-depth clinical research to verify the result.

Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.

Alzheimer's disease(AD)and Parkinson's disease(PD)are common neurodegenerative diseases that seriously threaten the health of the elderly, involving various abnormalities in physiology and metabolism including the impairment of mitochondrial function, Ca 2+ homeostasis deregulation, oxidative stress, aggregation of misfolded proteins, autophagy and inflammation.However, mechanisms underlying the pathogenesis of these diseases have not been clearly elucidated, thus impeding advances in their treatment.In recent years, it has been found that mitochondria-associated endoplasmic reticulum membranes(MAM)play an important role in the development of AD and PD and exert their effects by regulating the functions of mitochondria and endoplasmic reticula.This article reviews studies of the past decade related to the effects of MAM on AD and PD, aiming to generate insights for exploring the constituent proteins of MAM and the molecular mechanisms of AD and PD via endoplasmic reticulum-mitochondria Ca 2+ transport and ER stress regulated by MAM.

Objective:To explore the surgical outcomes and surgery-related complications of balanced orbital decompression and endoscopic transnasal inferomedial wall decompression for Grave's ophthalmopathy (GO).Methods:A cohort study was performed.The 56 GO patients who underwent balanced orbital decompression or endoscopic transnasal inferomedial wall decompression in the Tianjin Medical University Eye Hospital from December 2016 to December 2019 were enrolled.The follow-up time was 6 months.Patients were divided into two groups according to the operation modes.Thirty-three eyes of 24 subjects were given deep lateral wall rim-sparing orbital decompression and transcaruncular medial wall decompression, and 51 eyes of 36 cases were given endoscopic transnasal inferomedial wall decompression.The demographics, surgical details, imaging data, postoperative changes of exophthalmos, best corrected visual acuity (BCVA), orbital pressure and diplopia, surgery-related complications and further treatment were analyzed and compared.This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital [No.2020KY(L)-39]. All subjects signed informed consent.Results:The exophthalmos was (21.03±3.11)mm before operation, which was significantly higher than (17.06±2.55)mm after operation in the balanced orbital decompression group ( P<0.05). The exophthalmos was (20.51±3.53)mm before operation, which was significantly higher than (16.28±2.96)mm after operation in the endoscopic transnasal inferomedial wall decompression group ( P<0.05). No significant difference in the mean reduction of proptosis was found between the two groups ( P>0.05). All the subjects were accompanied with increase of intraorbital pressure before operation.The intraorbital pressure returned to normal at 6 months after operation.The postoperative BCVA of subjects with dysthyroid optic neuropathy (DON) were significantly higher than preoperative values ( Z=-3.524, -4.376; both at P<0.01). The postoperative improvement values of BCVA were 0.48 (0.25, 0.67) and 0.72 (0.40, 0.80) in the balanced orbital decompression group and the endoscopic transnasal inferomedial wall decompression group, respectively, with a significant difference between the two groups ( Z=-2.481, P=0.016). The incidence of complications in the balanced orbital decompression group was 21.2% (7/33), which was significantly lower than 47.0% (24/51) in the endoscopic transnasal inferomedial wall decompression group ( χ2=5.748, P=0.017). Conclusion:The two kinds surgical methods can effectively reduce the degree of exophthalmos and orbital pressure.Endoscopic transnasal inferomedial wall decompression can provide better improvement of visual function in patients with DON, but has a higher risk of surgery-related complications in comparison with the balanced orbital decompression.

Objective: To explore the effects of multidisciplinary comprehensive intervention in integrated treatment of patients with extremely severe burns. Methods: One hundred and ten patients hospitalized in our center from July 2013 to August 2017 met the criteria for inclusion in this study, and their medical records were retrospectively analyzed. According to the medical model at that time, 56 patients hospitalized from July 2013 to July 2015 received routine comprehensive treatment led by doctors, and they were included in the conventional intervention group. From August 2015 to August 2017, 54 patients were treated with integrated multidisciplinary interventions performed by a team consisting of physicians, intensive care nurses, burn nurses, intravenous infusion nurses, wound stoma nurses, and rehabilitation therapists, and they were included in the integrated intervention group. Acute Physiological and Chronic Health Assessment Ⅱ (APACHE Ⅱ) scores on admission and 4 weeks after treatment, incidences of pressure injury, wound sepsis, lung infection, and catheter-related infection during hospitalization, length of stay in intensive care unit (ICU) and total length of hospital stay, and Abbreviated Burn Specific Health Scale (BSHS-A) scores at discharge and 3 months after discharge were analyzed. Data were processed with t-test and chi-square test. Results: The APACHE Ⅱ scores of patients in the two groups were close on admission (t=0.573, P>0.05). Four weeks after treatment, the APACHE Ⅱ scores of patients in the two groups were obviously lower than those on admission within the same group (t=5.697, 4.853, P<0.01), and the score of the integrated intervention group was obviously lower than that of the conventional intervention group (t=2.170, P<0.05). No pressure injury was observed in patients of any group during hospitalization. The incidences of wound sepsis, lung infection, and catheter-related infection of patients in the integrated intervention group were 18.5% (10/54), 3.7% (2/54), and 9.3% (5/54), respectively, significantly lower than 42.9% (24/56), 21.4% (12/56), and 26.8% (15/56) of the conventional intervention group, χ²=4.073, 6.075, 3.962, P<0.05. The length of stay in ICU of patients in the integrated intervention group was (50±5) d, obviously shorter than (62±4) d of the conventional intervention group (t=2.852, P<0.01). The total length of hospital stay of patients in the integrated intervention group was (115±8) d, obviously shorter than (140±7) d of the conventional intervention group (t=16.885, P<0.01). At discharge and 3 months after discharge, the scores of BSHS-A, physical function, psychological function, and general health status of 50 patients in the integrated intervention group were significantly higher than those of 48 patients in the conventional intervention group (t=2.886, 3.126, 2.416, 2.544, 2.033, 3.471, 2.588, 2.210, P<0.05 or P<0.01), while the scores of social function of patients in the two groups were close (t=1.570, 1.350, P>0.05). Conclusions Integrative treatment of patients with extremely severe burns by multidisciplinary comprehensive intervention can significantly alleviate the severity of burns, reduce the incidences of wound sepsis, lung infection, and catheter-related infection, shorten the length of stay in ICU and total length of hospital stay, and improve the quality of life.