[A study on the burden of myocarditis in China in 1990 and 2019].

Objective: To investigate Chinese myocarditis burden and trends in 1990 and 2019. Methods: Based on the Global Burden of Disease (GBD) 2019 data, the number of patients, the number of new cases, the number of deaths, the disability-adjusted life years (DALYs), as well as the morbidity, mortality, DALYs rate and their age-standardized rates were used to analyze the trend and the burden of myocarditis in the Chinese population in 1990 and 2019. Results: In 2019, the number of patients, the number of new cases and the number of deaths with myocarditis in China were 234 900, 275 100 and 13 100 respectively, increasing by 85.62%, 47.51% and 50.22% compared with 1990. The age-standardized incidence and mortality were 16.94/100 000 and 0.92/100 000, respectively. Compared with 1990, the age-standardized incidence in 2019 decreased by 6.06%, and the mortality decreased by 16.04% respectively. The age-standardized incidence and mortality of Chinese male patients with myocarditis were higher than that of female. Compared with 1990, the age group with the largest incidence and mortality of myocarditis in China in 2019 all shifted to the elder group. And, DALYs and age-normalized DALYs due to myocarditis in China showed a decreasing trend in 2019, from 458 600 and 42.51/100 000 in 1990 to 341 300 and 25.39/100 000 in 2019, respectively. The rate of DALYs and age-standardized DALYs in male patients was always higher than female. Conclusions: Compared with 1990, the overall burden of myocarditis in China showed a downward trend in 2019, and the burden of myocarditis in male patients was higher than female. More attention should be paid to the burden of myocarditis in Chinese elderly population.

[WWP1 promotes cell proliferation in hepatocellular carcinoma through ubiquitin-degradation EI24].

Objective: To screen the interaction proteins of WW domain containing protein 1 (WWP1), and explore the effects of WWP1 and etoposide induced 24 (EI24) on cell proliferation in hepatocellular carcinoma (HCC). Methods: Yeast two-hybrid screening system was used to identify the interaction proteins of WWP1. The interaction was further validated by co-immunoprecipitation. WWP1 and EI24 stably over-expressing or deleted HepG2 cells were established by using the lentivirus transduction method. Colony forming assay and cell counting kit-8 (CCK8) assay were performed to identify the effects of WWP1 and EI24 on cell proliferation. In addition, the role of WWP1 in the tumorigenicity of liver cancer in vivo was examined by subcutaneous injection of different level of WWP1 expressed HepG2 into nude mice. Results: WWP1 can interact with EI24 and ubiquitin-degrade EI24 protein. The WWP1 and EI24 over-expressing or deleted HepG2 cell lines were successfully generated. Overexpression of WWP1 decreased while knockdown of WWP1 increased the protein level of EI24. The results of CCK-8 assay showed that the relative proliferation activities of WWP1 overexpressed (WWP1-OE) group and WWP1 knockdown (shWWP1) group on 36 hours were (347.00±8.15)% and (187.08±4.86)%, respectively, significantly different from (270.33±15.01)% of control group (both P<0.05). The relative proliferation activities of EI24 overexpressed (EI24-OE) group and EI24 knockdown (shEI24) group on 36 hours were (183.75±8.11)% and (317.33±9.60)%, respectively, significantly different from (270.33±15.01) % of control group (both P<0.05). The results of colony formation assay showed that the colony numbers of control group, WWP1-OE group and shWWP1 group were (52±7)/visual field (VF), (76±4)/VF, (19±3)/VF, respectively. Overexpression of WWP1 significantly increased while knockdown of WWP1 significantly decreased the colon formation ability of HepG2 cells (both P<0.05). The colon number of control group, EI24-OE group and shEI24 group were (38±4)/VF, (10±3)/VF, (69±7)/VF, respectively. Overexpression of EI24 significantly decreased while knockdown of EI24 significantly increased the colony formation ability of HepG2 cells (both P<0.05). The results of xenograft mice model showed that the tumor volumes of control, WWP1-OE, and shWWP1 group were (1 400.00±43.71)mm(3,) (2 636.67±290.45) mm(3) and (642.17±36.00)mm(3,) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.23±0.08)g, (2.05±0.17)g, and (0.88±0.09)g, respectively, with significant differences (P<0.05). The tumor volumes of control, EI24-OE, and shEI24 group were (1 245.17±93.10)mm(3,) (662.17±60.88)mm(3) and (1 986.67±226.75)mm(3) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.15±0.04)g, (0.85±0.02)g and (1.73±0.05)g respectively, with significant difference (P<0.05). Conclusion: WWP1 promote the cell proliferation of liver cancer through ubiquitin-degradation of EI24.

[Malfunction of autophagy in tibial growth plate chondrocytes causes increased apoptosis rate in chronic renal insufficiency rats].

Objective: To observe the effect of autophagy of tibial growth plate chondrocyte on apoptosis in chronic renal insufficiency (CRI) rats. Methods: Male 4-week-old SD rats were randomly divided into two groups: (1) Sham group: only the left ureter was exposed (n=10); (2) CRI group: the left ureter was ligated to cause CRI (n=10). The urine from all the rats was collected 6 weeks after the operation and the total protein content was measured. Then all the rats were sacrificed and the concentrations of creatinine and urea nitrogen in intracardiac blood were detected. The proximal tibia were fixed and decalcified to prepare histological sections, and the number of chondrocytes of column cells in the proliferative area of tibia growth plate was observed by saffron O staining. The expression rate of protein Light Chain-3, an autophagy marker of chondrocytes, was detected by immunofluorescence. The apoptosis rate of chondrocytes was detected by the method of TUNEL assay. The level of glycogenin-1, a glycogen formation marker of chondrocyte was detected by immunohistochemistry in chondrocytes. Results: The 24 h urine total protein was higher in CRI group [(163.5±11.3) mg vs (38.6±9.8) mg, t=25.620, P<0.001]. The levels of blood creatinine [(67.3±16.2) µmol/L vs (28.4±11.5) µmol/L, t=5.974, P<0.001] and urea nitrogen [(16.4±6.4) mmol/L vs (4.8±2.0) mmol/L, t=5.198, P<0.001] were higher in CRI group. The number of chondrocytes of column cells in the proliferating area of tibia growth plate was lower in CRI group (4.2±2.1 vs 9.1±3.8, t=3.109, P=0.006). The expression rate of LC-3 protein in chondrocytes of CRI group was lower [(27.2±12.6)% vs (51.4±18.2)%, t=3.457, P=0.003]. The level of glycogenin-1 of chondrocytes in CRI group increased significantly (6.1±2.5 vs 3.5±1.8, t=2.669, P=0.016). The apoptosis rate of chondrocytes in CRI group also increased [(17.2±4.8)% vs (5.1±3.4)%, t=6.505, P<0.001]. Conclusion: Malfunction of autophagy in tibial growth plate chondrocytes causes increased apoptosis rate in CRI rats, which might be caused by the failure of glycogen degradation in chondrocytes.

[The inhibition effects of apatinib on cell proliferation, migration and apoptosis in esophageal carcinoma via Ras/Raf/MEK/ERK and JAK2/STAT3 pathways].

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 µmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 µmol/L and 40 µmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 µmol/L, 20 µmol/L and 40 µmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 µmol/L and 40 µmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 µmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 µmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

[Experimental study on the improvement of Ilizarov transverse tibial bone transport and microcirculation reconstruction technique].

Objective: To observe the effect of traditional and modified Ilizarov transverse tibial bone transport on microvascular regeneration of lower limbs in dogs. Methods: After general anesthesia on 10 experimental dogs, traditional and modified transverse tibial bone transport were performed on both tibias respectively. The control group was treated with the traditional method (the periosteum and bone flap were completely isolated), while the experimental group was treated with the modified method (the fibular periosteum of the open window bone flap was retained). All the external fixators were pulled outwards at a speed of 1 mm every day from 5 days after operation;after one week, the external fixators were moved back every 3 days for one week. The situation of wounds and activity of lower limbs were observed. Simultaneously, the angiogenesis was observed by digital subtraction angiography (DSA) through femoral artery at different stages, and the density of vascular endothelial cells measured by local tissue sections. The data before and after the operation were compared with paired t test. Results: The operation was successfully completed in 10 experimental dogs, and all wounds healed about 1 week after the operation. There was no significant abnormality in lower limb movements in all dogs. Peripheral blood vessel area in middle leg of lower limb in 4 weeks and 8 weeks after operation was (5.9±0.4) mm(2) and (6.9±0.6) mm(2) in control group and it was (6.2±0.6) mm(2) and (8.0±0.6) mm(2) in experimental group, respectively; all were significantly improved than those before the operation ((5.0±0.4) mm(2), (4.9±0.4) mm(2), respectively) (F=446.457, 829.192, both P<0.05). There was no significant differences in vessel area between the two groups at the 4th week after operation (t=1.216, P=0.240), but there was significant difference at the 8th week after operation between the two groups (t=4.423, P=0.000). The percentage of vascular endothelial cells in stained cells under endoscopy was 4.42%±0.28% and 5.63%±0.53% in the control group at the 8th week; and in the experimental group, it was 5.35%±0.26% and 7.18%±0.25%, respectively;all were significantly elevated than those before the operation; and there were significant differences between the two groups (t=7.35, 8.30, both P<0.05). Conclusion: Transverse tibial bone transport and microvascular network regeneration technology can reconstruct the microvasculature below the calf of dogs; the method of window-opening osteotomy is improved to "door" type window-opening, it can retain the lateral periosteum of tibial crest and regenerate the microvasculature network more abundantly.

[Effect of low expression of PTHrp receptor on proliferation of tibial growth plate chondrocytes in chronic renal insufficiency young rats].

Objective: To observe the effect of parathyroid hormone-related protein (PTHrp) receptor on the proliferation of tibial growth plate chondrocytes in chronic renal insufficiency (CRI) young rats. Methods: Two-week-old male SD rats were randomly divided into two groups: (1) Sham group (n=6), only left ureter was exposed; (2) CRI group(n=6), left ureter was ligated to induce chronic renal insufficiency. Rats were sacrificed 2 weeks after operation and the blood concentration of PTHrp was detected by intracardiac blood sampling. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. The level of PTHrp receptor in chondrocytes was observed by immunohistochemistry and quantitative analysis was completed by Western blot. The proliferation rate of chondrocytes from two groups at 24 h was detected by using 5-ethynyl-2'-deoxyuridine (EDU) technique. Three types of PTHrp receptor mRNA plasmids (overexpressed, empty vector and knockdown) were used to treat the chondrocytes from CRI group. The mRNA and protein levels of PTHrp receptor were detected after 24 h and 48 h intervention, respectively. The chondrocyte proliferation rate at 24 h was detected by EDU. Results: Blood concentration of PTHrp in CRI group was higher than that in Sham group [(1.36±0.42) ng/L vs (0.77±0.21) ng/L, t=3.913, P=0.001]. The results of Western blot showed that the level of PTHrp receptor in growth plate chondrocytes from CRI group decreased (0.15±0.07 vs 0.41±0.13, t=5.569, P<0.001). Chondrocyte proliferation rate of CRI group was lower than that in Sham group at 24 h [(11.3±3.1)% vs (24.6±5.7)%, t=6.482, P<0.001]. The mRNA and protein levels of PTHrp receptor increased in chondrocytes of CRI group after intervention with overexpressed plasmid. The chondrocyte proliferation rate increased at 24 h. On the contrary, the mRNA and protein levels of PTHrp receptor decreased afer intervention with knockdown plasmid, and the chondrocyte proliferation rate also decreased [overexpression: (22.8±6.5)%, empty carrier: (10.2±4.3)%, knockdown: (5.6±2.1)%, F=29.840, P<0.001]. Conclusion: Increased PTHrp concentration in the blood of CRI young rats leads to decreased PTHrp receptors in growth plate chondrocytes, which results in decreasing PTHrp activity and proliferation rate of chondrocyte.

[Next generation sequencing technology for susceptible gene screening in familial non-medullary thyroid carcinoma].

Objective: To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS). Methods: A panel of NGS was designed and sequencing was performed for DNA samples extracted from peripheral blood leukocytes of FNMTC patients and sporadic non-medullary thyroid carcinoma (SNMTC) cases, respectively, and gene mutations were screened. In addition, the clinicopathological characteristics, including tumor size, extension of surgery, lymph node metastasis and extra-thyroidal extension, were compared between patients with or without mutations. Results: In 63 NMTC samples, 45 mutations were detected on 13 genes. 37 germline mutations were detected in 47 FNMTC patients, while 8 germline mutations were detected in 16 SNMTC patients. In 8 FNMTC family lineages, the same mutations were carried by FNMTC patients from the same pedigree. The number of carriers of mutations was 29 in the 47 FNMTC patients and 6 in the 16 SNMTC patients, with a non-significant difference (P= 0.092). Among the FNMTC patients, there were 22 patients with central lymph node metastasis in the 29 mutation-positive patients, significantly more than 7 in the 16 mutation-negative cases (P= 0.031). As for the parentage, there were 3 patients with central lymph node involvement among the 7 patients of parent generation, while all the 9 patients of offspring generation had central lymph node metastasis (P=0.019). Conclusions: This panel of NGS can be used to screen mutant susceptibility gene of FNMTC patients, and the findings may be helpful for early detection of FNMTC patients and predicting the disease risk to familial members of FNMTC patients.

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t-test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference (P=0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV (P=0.002). The difference of D(90) was similarly (P<0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

[Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma].

OBJECTIVE: To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor (VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients. METHODS: One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control. RESULTS: Among the eighty-nine patients evaluable, the 1- and 3-year overall survival (OS) rates were 70.8% and 33.3%, respectively; 1-year and 3-year progression-free survival (PFS) rates were 61.8% and 28.2%, respectively; and 1-year and 3-year local control (LC) rates were 76.9% and 50.0%, respectively. The 1-year OS rates in the patients with mild, moderate and intensive pathological responses were 50.0%, 76.9% and 78.0%, respectively. The 1-year OS rate in the mild response group was significantly lower than that in the intensive response group (P<0.05). The 1-year and 3-year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0.0%, 40.0% and 38.9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups(P<0.05 for both). Moreover, the 1-year local control (LC) rates in the three groups were 52.9%, 83.3% and 83.8%, and the three-year LC rates were 0.0%, 64.3% and 64.0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy (F=6.124, P=0.004). The 1-year OS rates in the VEGF-increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3-year OS rates in these three groups were 15.4%, 27.0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF-decreased group (P<0.05). Moreover, the 3-year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF-increased group was significantly lower than that in the VEGF-decreased group (P<0.05). The multi-variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non-surgical patients with esophageal cancer (P<0.05 for all). CONCLUSIONS: Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non-surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.

Diagnostic Accuracy and Failure Mode Analysis of a Deep Learning Algorithm for the Detection of Cervical Spine Fractures.

BACKGROUND AND PURPOSE: Artificial intelligence decision support systems are a rapidly growing class of tools to help manage ever-increasing imaging volumes. The aim of this study was to evaluate the performance of an artificial intelligence decision support system, Aidoc, for the detection of cervical spinal fractures on noncontrast cervical spine CT scans and to conduct a failure mode analysis to identify areas of poor performance. MATERIALS AND METHODS: This retrospective study included 1904 emergent noncontrast cervical spine CT scans of adult patients (60 [SD, 22] years, 50.3% men). The presence of cervical spinal fracture was determined by Aidoc and an attending neuroradiologist; discrepancies were independently adjudicated. Algorithm performance was assessed by calculation of the diagnostic accuracy, and a failure mode analysis was performed. RESULTS: Aidoc and the neuroradiologist's interpretation were concordant in 91.5% of cases. Aidoc correctly identified 67 of 122 fractures (54.9%) with 106 false-positive flagged studies. Diagnostic performance was calculated as the following: sensitivity, 54.9% (95% CI, 45.7%-63.9%); specificity, 94.1% (95% CI, 92.9%-95.1%); positive predictive value, 38.7% (95% CI, 33.1%-44.7%); and negative predictive value, 96.8% (95% CI, 96.2%-97.4%). Worsened performance was observed in the detection of chronic fractures; differences in diagnostic performance were not altered by study indication or patient characteristics. CONCLUSIONS: We observed poor diagnostic accuracy of an artificial intelligence decision support system for the detection of cervical spine fractures. Many similar algorithms have also received little or no external validation, and this study raises concerns about their generalizability, utility, and rapid pace of deployment. Further rigorous evaluations are needed to understand the weaknesses of these tools before widespread implementation.

miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells, by J.-J. Wang, J.-P. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2497-2504-DOI: 10.26355/eurrev_201903_17397-PMID: 30964176" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17397.

[Loss of autophagy in condylar chondrocytes causes increased apoptosis rate in temporomandibular joint osteoarthritis of rats].

Objective: To observe the effect of autophagy of condylar chondrocytes on apoptosis in temporomandibular joint osteoarthritis (TMJOA) of rats. Methods: Fourty male 2-month-old SPF SD rats were equally divided into sham group (n=20) and experimental group (n=20). UAC metal prosthesis was cemented to the left incisors of maxilla and mandible of the rats in experimental group rats. After 8 weeks, all rats were sacrificed and the temporomandibular joint was taken. Two groups of rat condylar chondrocytes were extracted and cultured in vitro to the third generation. Immunofluorescence technique was used to detect the levels of collagen Ⅱ and matrix metalloproteinase-13 (MMP-13) in chondrocytes. The level of light chain-3 (LC-3), an autophagy marker of chondrocytes, was detected. Immunohistochemical technique was used to detect the level glycogenin-1, a glycogen formation marker of chondrocyte, was detected. The level of caspase-3, an apoptosis marker of chondrocyte, was also detected. Tunel technique was used to detect the apoptosis rate of the two groups at 72 h. Cracking cell extraction of total protein, Western-blotting (WB) technology to detect the levels of collagen Ⅱ, MMP -13, LC-3, glycogenin-1, caspase-3 and make gray analysis. Results: Compared with sham group, the level of collagen Ⅱ decreased, MMP-13 increased, LC-3 decreased, glycogenin-1 increased and caspase-3 increased in experimental group. The apoptosis rate of chondrocytes in experimentaal group [ (17.3±4.4) %] at 72h was higher than that in control group [ (5.6±2.1) %](t=10.732, P<0.001) .WB bands gray statistical results show that the level of collagen Ⅱ in chondrocytes of experimental group (0.43±0.21) was lower than that of control group (0.71±0.26) (t=2.409, P=0.043) , the level of MMP-13 in chondrocytes of experimental group (0.73±0.31) was higher than that of control group (0.24±0.10) (t=3.364, P=0.010) , the level of LC-3 in chondrocytes of experimental group (0.09±0.04) was lower than that of control group (0.39±0.18) (t=3.638, P=0.007) , the level of glycogenin-1 in chondrocytes of experimental group (0.68±0.30) was higher than that of control group (0.29±0.17) (t=2.529, P=0.035) , the level of caspase-3 in chondrocytes of experimental group (0.19±0.08) was higher than that of control group (0.05±0.02) (t=3.796, P=0.005) . Conclusions: The level of autophagy of condylar chondrocytes in temporomandibular joint of rats decreased, glycogen accumulation increased, the rate of chondrocyte apoptosis increased, and the number of chondrocytes decreased, resulting in degeneration of condylar cartilage tissue.

miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells.

OBJECTIVE: MAPK kinase 1 (MEK1), also known as MAP2K1, plays a role in activating extra-cellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway to regulate cell proliferation and apoptosis. The abnormal expression of MAP2K1 is associated with leukemia. Bioinformatics analysis showed the targeted relationship between microRNA-181a (miR-181a) and the 3'-UTR of MAP2K1. This study aimed to investigate the role of miR-181a in regulating MAP2K1 expression, the effects on leukemic cell proliferation, apoptosis, and adriamycin (ADM) resistance. MATERIALS AND METHODS: Dual luciferase reporter gene assay was applied to confirm the targeted relationship between miR-181a and MAP2K1. ADM resistant cell line HL-60/ADM was established. MiR-181a and MAP2K1 expressions were detected. HL-60/ADM cells were cultured in vitro and divided into two groups, including microRNA-Normal control (miR-NC) group and miR-181a mimic group. MAP2K1, phosphorylated MAP2K1 (p-MAP2K1), and phosphorylated ERK (p-ERK) protein expressions were tested. Cell apoptosis was assessed with flow cytometry. Cell proliferation was determined using EdU staining. RESULTS: There is a targeted regulatory relationship between miR-181a and MAP2K1 mRNA. miR-181a expression was significantly lower, while MAP2K1 mRNA and protein expressions were markedly higher in HL-60/ADM cells than HL-60 cells (p<0.05). Transfection of miR-181a mimic markedly reduced expressions of MAP2K1, p-MAP2K1, and p-ERK in HL-60/ADM cells, enhanced cell apoptosis, and weakened cell proliferation compared to miR-NC (p<0.05). CONCLUSIONS: MiR-181a reduction and MAP2K1 elevation were related to ADM resistance in leukemia cells. Up-regulation of miR-181a expression inhibited leukemia cell proliferation, induced apoptosis, and reduced ADM resistance via targeting MAP2K1 expression and ERK/MAPK signaling pathway.

[Status of health examination on public health employees in Beijing].

Objective: The aim of this study was to understand the status of health examination on public health employees in Beijing, in order to further standardize the health management of the employees. Methods: Questionnaire surveys and personal interviews were produced to obtain the basic information, physical examination, occupational training, knowledge of health laws and regulations, and satisfaction of employees. Pairwise comparison was conducted by chi-square test. Multivariate linear regression was used for multivariate analysis. Results: The percentage of the public health employees who took the blood tests, X-ray examinations, fecal examinations, and skin examinations were 97.0%, 77.6%, 86.4%, and 51.0%, respectively. After excluding the skin examination, the completion rate of other examination items was 72.1%, and the difference of this rate between public hospitals and private hospitals were statistically significant (χ(2)=36.22, P<0.001; χ(2)=9.09, P=0.003; χ(2)=31.06, P<0.001). The percentage of correct answers to all the five questions was 3.2%, and age, working age and education level were positively correlated with knowledge scores of employees. Conclusions: The problems in Beijing's health examination of employees included poor examination quality, lack of supervision, inability to trace the source and low awareness rate of health knowledge, which suggested that counter measures should be taken immediately.

Midline preperitoneal repair for incarcerated and strangulated femoral hernia.

OBJECTIVE: Femoral hernias constantly present as incarceration or strangulation and require emergency surgery. Incarcerated and strangulated femoral hernia repair remains challenging and controversial. The aim of our study was to analyze the efficacy of preperitoneal tension-free hernioplasty via lower abdominal midline incision for incarcerated and strangulated femoral hernia. METHODS: Data of 47 patients who underwent emergency surgery for incarcerated or strangulated femoral hernias from January 2009 to December 2017 were retrospectively analyzed. According to the surgical incisions, they were divided into two groups: the observation group (21 cases) had a lower abdominal midline incision, and the control group (26 cases) had a traditional inguinal incision. General data of patients, intraoperative findings, operative time and postoperative complications were compared. RESULTS: Patient characteristics showed that the two groups were comparable.15 cases (31.9%) underwent intestinal resection, and 32 cases (68.1%) underwent first-stage tension-free repair in total. The rate of first-stage tension-free hernioplasty was significantly higher in the observation group (18/21, 85.7% vs 14/26 53.8%, P = 0.020). No additional incision was required in the observation group, while six cases of the control group (23.1%) had an additional incision for intestinal resection and anastomosis (P = 0.026). Mean operative time (53.6 ± 24.7 min vs 77.9 ± 36.5 min, P = 0.012) and the length of hospital stay (6.3 ± 4.2 days vs 10.3 ± 6.9 days, P = 0.020) were significantly shorter in the observation group. The time of return to normal physical activity resulted significantly reduced compared to the control group (9.2 ± 4.1 days vs 13.3 ± 6.6 days, P = 0.017). The total incidence of postoperative complication (including chronic pain, foreign body sensation, hernia recurrence, wound infection and seroma/hematomas) in the observation group was lower (14.3% vs 42.3% P = 0.037). There were two recurrences in the control group. No mesh-related infection and no mortalities in two groups. CONCLUSIONS: Midline preperitoneal approach for incarcerated and strangulated femoral hernia is a convenient and effective technique. It can improve the rate of first-stage tension-free repair of incarcerated femoral hernia and allow intestinal resection through the same incision, and with lower rate of postoperative complications.

Contrast-Enhanced 3D-FLAIR Imaging of the Optic Nerve and Optic Nerve Head: Novel Neuroimaging Findings of Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: The sensitivity of contrast-enhanced 3D-FLAIR has not been assessed in patients with idiopathic intracranial hypertension. The purpose of this study was to evaluate whether hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR imaging is associated with papilledema in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: A retrospective review was conducted from 2012 to 2015 of patients with clinically diagnosed idiopathic intracranial hypertension and age- and sex-matched controls who had MR imaging with contrast-enhanced 3D-FLAIR. Two neuroradiologists graded each optic nerve/optic nerve head on a scale of 0-3. This grade was then correlated with the Frisén Scale, an ophthalmologic scale used for grading papilledema from 0 (normal) to 5 (severe edema). To estimate the correlation between the MR imaging and Frisén scores, we calculated the Kendall τ coefficient. RESULTS: Forty-six patients (3 men, 43 women) with idiopathic intracranial hypertension and 61 controls (5 men, 56 women) with normal findings on MR imaging were included in this study. For both eyes, there was moderate correlation between the 2 scales (right eye: τ = 0.47; 95% CI, 0.31-0.57; left eye: τ = 0.38; 95% CI, 0.24-0.49). Interreader reliability for MR imaging scores showed high interreader reliability (right eye: κ = 0.76; 95% CI, 0.55-0.88; left eye: κ = 0.87; 95% CI, 0.78-0.94). Contrast-enhanced 3D-FLAIR imaging correlates with the Frisén Scale for moderate-to-severe papilledema and less so for mild papilledema. CONCLUSIONS: Hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR is sensitive for the detection of papilledema in patients with idiopathic intracranial hypertension, which may be useful when prompt diagnosis is crucial.

A safe and efficient strategy for endoscopic resection of large, gastrointestinal lipoma.

BACKGROUND: Gastrointestinal (GI) lipomas are benign, slowly growing, submucosal tumors, which may cause gastrointestinal bleeding, anemia, intussusception, and bowel obstruction. The aim of this study is to explore the safe and effective strategy for endoscopic removal of large GI lipomas. METHODS: During last 10 years, fifteen large and symptomatic GI lipomas were resected under endoscopy in our hospital. In them, two large lipomas with small stalk (< 2 m in diameter) were resected by polypectomy; ten large lipomas with base size greater than 2 cm in diameter were removed using a "subtotal resection." Three other large lipomas with small stalk (< 2 m in diameter) were resected by multistep resection. Endoscopic ultrasonography (EUS) and miniprobe endoscopic ultrasound were performed in six cases from January 2000 to July 2004 to confirm that those lesions were lipomas that were superficial to the muscularis propria. RESULTS: All 15 lesions were successfully removed and were histopathologically confirmed to be lipomas. No severe complications, such as perforation or hemorrhage, developed after endoscopic removal. No recurrence was observed after 1-8 years follow-up endoscopic examination. CONCLUSIONS: Various, large GI lipomas can be removed safely by electrosurgical snare resection under endoscopy following the guidance of the present therapeutic strategy.

Activation of Akt and ERK signalling pathways induced by etoposide confer chemoresistance in gastric cancer cells.

AIMS: To identify whether phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways are implicated in the chemoresistance of gastric cancer and to explore the possible mechanisms. METHODS: Gastric cancer cell lines SGC7901 and BGC823 were exposed to etoposide, Wortmannin+etoposide or PD98059+etoposide. Cell cycle distribution and cell apoptosis were detected using flow cytometry and Hoechst 33258 staining. Cells viability was determined by a colourimetric assay utilising 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Akt activity was detected using non-radioactive immunoprecipitation-kinase assay. Western blotting was exploited to evaluate the level of phosphorylated ERK1/2 and expressions of c-Myc and p53 protein. RESULTS: Etoposide suppressed the viability of SGC7901 and BGC823 cells in a time- and dose-dependent manner; PD98059 and Wortmannin were able to enhance the cytotoxicity of etoposide. The apoptotic levels of cells treated with Wortmannin+etoposide or PD98059+etoposide were significantly higher than those of cells treated with etoposide only. Phospho-ERK1/2, Akt activity and expression of c-Myc were significantly induced by etoposide in a time-dependent manner; moreover, there was a weak effect on the expression of p53 protein. Both Wortmannin and PD98059 elevated the level of p53 expression strikingly, however, only PD98059 suppressed the up-regulation trend of c-Myc expression induced by etoposide. CONCLUSION: Chemotherapy reagent activated phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways, which decreased the chemotherapy sensitivity of gastric cancer cell lines SGC7901 and BGC823 via suppressing the expression of p53 and enhancing the expression of c-Myc. This may be one of the molecular mechanisms of gastric cancer chemoresistance.