[Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil].

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

[A case of pleural metastasis of malignant peripheral nerve sheath tumor].

Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.

HER2-low expression in patients with advanced or metastatic solid tumors.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined category with HER2 1+ or 2+ expression by immunohistochemistry (IHC) and lack of HER2 gene amplification measured by in situ hybridization (ISH). Much remains unknown about the HER2-low status across tumor types and changes in HER2 status between primary and metastatic samples. PATIENTS AND METHODS: HER2 expression by IHC was evaluated in 4701 patients with solid tumors. We have evaluated the HER2 expression by IHC and amplification by ISH in paired breast and gastric/gastroesophageal (GEJ) primary and metastatic samples. HER2 expression was correlated with ERBB2 genomic alterations evaluated by next-generation sequencing (NGS) in non-breast, non-gastric/GEJ samples. RESULTS: HER2 expression (HER2 IHC 1-3+) was found in half (49.8%) of the cancers, with HER2-low (1 or 2+) found in many tumor types: 47.1% in breast, 34.6% in gastric/GEJ, 50.0% in salivary gland, 46.9% in lung, 46.5% in endometrial, 46% in urothelial, and 45.5% of gallbladder cancers. The concordance evaluation of HER2 expression between primary and metastatic breast cancer samples showed that HER2 3+ remained unchanged in 87.1% with a strong agreement between primary and metastatic samples, with a weighted kappa (Κ) of 0.85 (95% confidence interval 0.79-0.91). ERBB2 alterations were identified in 117 (7.5%) patients with non-breast, non-gastric/GEJ solid tumors who had NGS testing. Of 1436 patients without ERBB2 alterations, 512 (35.7%) showed any level HER2 expression by IHC. CONCLUSION: Our results show that HER2-low expression is frequently found across tumor types. These findings suggest that many patients with HER2-low solid tumors might benefit from HER2-targeted therapies.

The prognostic value of splenic abnormalities in pretreatment 18F-FDG PET/CT in patients with complete response diffuse large B-cell lymphoma.

AIM: To investigate whether spleen imaging characteristics of baseline 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) can help to predict the clinical outcome in complete response (CR) diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Three hundred and six patients with DLBCL were enrolled in the study and divided into recurrence and non-recurrence groups. The splenic abnormalities were compared using the chi-square test and quantitative indexes were compared using the t-test. The Cox proportional hazard regression model was used for univariate and multivariate analysis. Kaplan-Meier curves and log-rank tests were used to compare progression-free survival (PFS). Propensity score matching (PSM) was used to match patients with and without splenic abnormalities according to age, gender, and initial Ann Arbor stage at a 1:2 ratio (52:104); then the recurrence and PFS results were compared again. RESULTS: Age, international prognostic index (IPI), stage, splenomegaly, and focal splenic lesions were significantly different between the recurrence and non-recurrence groups. IPI, stage, baseline spleen mean standard uptake value (SUVmean)/liver SUVmean, splenomegaly, and focal lesions were selected by Cox single-factor analysis, and only focal lesions showed a statistical difference in terms of Cox multivariate analysis (p=0.022, hazard ratio [HR]: 2.843). After PSM, focal splenic lesions (n=20) were still statistically different (p=0.003) between the recurrence and non-recurrence groups, and this played an essential role in PFS forecasting (p=0.0004, HR: 3.767). CONCLUSION: Focal splenic lesions were identified as an independent risk factor for the prognosis of DLBCL. Pretreatment splenomegaly and focal splenic lesions appeared to be related to the relapse and PFS of DLBCL patients. Focal splenic lesions still showed meaningful predictive value even with propensity matching.

Exploration of 68Ga-labelled prostate-specific membrane antigen-11 PET/CT parameters for identifying PBRM1 status in primary clear cell renal cell carcinoma.

AIM: To investigate the predictive value of 68Ga-labelled prostate-specific membrane antigen-11 (68Ga-PSMA-11) integrated positron-emission tomography (PET)/computed tomography (CT) in PBRM1-deficient clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A total of 41 patients with ccRCC, were enrolled retrospectively and underwent 68Ga-PSMA-11 PET/CT preoperatively. Radiological parameters, including CT attenuation value and maximum standard uptake value (SUVmax), were derived. Immunohistochemical and multiple immunofluorescences staining were performed to evaluate the PBRM1 status and immune response. The predictive value of imaging factors was analysed using a receiver operator characteristic curve analysis. Univariate and multivariate logistic regression analyses were used to investigate the relationship between clinical and radiological variables and PBRM1 status. RESULTS: A total of 41 patients were included in this study, with 14 patients having PBRM1-deficient status. The tumour diameter on imaging and SUVmax differed significantly in patients with different PBRM1 expression statuses and no difference in CT attenuation was identified. Univariate and multivariate logistic regression analyses showed SUVmax was an obvious predictor for identification of PBRM1-deficient tumours. In addition, PBRM1-deficient tumours tended to be accompanied by greater cytotoxic T-cell infiltration, although most of them were in an exhausted state. CONCLUSIONS: 68Ga-PSMA-11 PET/CT could be used to discriminate invasive PBRM1-deficient ccRCC.

Reactive cutaneous capillary endothelial proliferation predicted the efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

BACKGROUND: Reactive cutaneous capillary endothelial proliferation (RCCEP), a special adverse event (AE) only observed in patients treated with camrelizumab, was reported to be correlated with the efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. This study to analyze the possible correlation between the occurrence of RCCEP and efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). MATERIAL AND METHODS: In this study, we retrospectively analyzed the efficacy and RCCEP occurrence of camrelizumab in 58 patients with R/M HNSCC in the Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University School of Medicine between January 2019 and June 2022. Kaplan-Meier analysis was used to assess the correlation between the occurrence of RCCEP and the survival of enrolled patients, and COX multifactor analysis was adopted to evaluate associated factors that affected the efficacy of camrelizumab immunotherapy. RESULTS: A significant correlation between the incidence of RCCEP and a higher objective response rate was observed in this study (p=0.008). The occurrence of RCCEP was associated with better median overall survival (17.0 months vs. 8.7 months, p<0.0001, HR=5.944, 95% CI:2.097-16.84) and better median progression-free survival (15.1 months vs. 4.0 months, p<0.0001, HR=4.329,95% CI:1.683-11.13). In COX multifactor analysis, RCCEP occurrence was also an independent prognostic factor affecting OS and PFS in patients with R/M HNSCC. CONCLUSIONS: The occurrence of RCCEP can show a better prognosis, it could be used as a clinical biomarker to predict the efficacy of camrelizumab treatment.

[Effects of surface treatment on the phase and fracture strength of yttria- and magnesia-stabilized zirconia implants].

OBJECTIVE: To evaluate the effects of surface treatment on the phase and fracture strength of yttria-and magnesia-stabilized and its mechanisms. METHODS: One-piece cylindrical screw-type implants were fabricated with yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and magnesia partially stabilized zirconia (Mg-PSZ) using computer aided design (CAD)/computer aided manufacture (CAM) technique.They were divided into three groups: (1) placed in water for 1 h after final sintering (control group), (2) sandblasting using 110 µm Al2O3 particles, (3) sandblasting plus etching with hydrofluoric acid for 1 h.The surface morphology and roughness of the implants were evaluated.Tetragonal to monoclinic transformation was measured on the surface by X-ray diffraction.Static tests of the zirconia implants were carried out at room temperature following the International Standards Organization (ISO)14801:2014 Standard. RESULTS: Both sandblasting alone and sandblasting plus acid etching significantly increased surface roughness (Ra) of Mg-PSZ and Y-TZP implants (P < 0.01), with sandblasting plus acid etching exhibited the highest surface roughness.No monoclinic band was detected in Mg-PSZ surface.Compared with the control group, the surface monoclinic content of Mg-PSZ had no obvious change after surface treatments.However, strong monoclinic bands appeared in surface modified Y-TZP.Monoclinic content of Y-TZP was higher than that of control group (1.55%) after both sandblasting alone (16.44%) and sandblasting plus acid etching (7.68%).For Mg-PSZ implants, fracture strengths of sandblasting group and sandblasting plus acid etching group were (294.1±3.3) N and (331.3±26.4) N respectively, which were lower than that of control group (458.4±48.7) N with significant differences (P < 0.01).For Y-TZP implants, fracture strength of control group was (827.3±101.6) N.Compared with control group, sandblasting group showed significantly higher fracture strength (P=0.03), which was (1 162.9±116.5) N.While sandblasting plus acid etching group had a fracture strength of (867.2±171.0) N, with no significant difference with control group (P>0.99). CONCLUSION: Sandblasting improved the fracture strength of Y-TZP implants.For the Mg-PSZ implants manufactured in this study, surface treatments with sandblasting and sandblasting plus acid etching resulted in a decrease of fracture strength.

[Effect of porous zirconia ceramics on proliferation and differentiation of osteoblasts].

OBJECTIVE: To investigate the effect of porous surface morphology of zirconia on the proliferation and differentiation of osteoblasts. METHODS: According to different manufacturing and pore-forming methods, the zirconia specimens were divided into 4 groups, including milled sintering group (M-Ctrl), milled porous group (M-Porous), 3D printed sintering group (3D-Ctrl) and 3D printed porous group (3D-Porous). The surface micromorphology, surface roughness, contact angle and surface elements of specimens in each group were detected by scanning electron microscope (SEM), 3D laser microscope, contact angle measuring device and energy-dispersion X-ray analysis, respectively. MC3T3-E1 cells were cultured on 4 groups of zirconia discs. The cell morphology of MC3T3-E1 cells on zirconia discs was eva-luated on 1 and 7 days by SEM. The cell proliferation was detected on 1, 3 and 5 days by cell counting kit-8 (CCK-8). After osteogenic induction for 14 days, the relative mRNA expression of alkaline phosphatase (ALP), type Ⅰ collagen (Colla1), Runt-related transcription factor-2 (Runx2) and osteocalcin (OCN) in MC3T3-E1 cells were detected by real-time quantitative polymerase chain reaction. RESULTS: The pore size [(419.72±6.99) µm] and pore depth [(560.38±8.55) µm] of 3D-Porous group were significantly larger than the pore size [(300.55±155.65) µm] and pore depth [(69.97±31.38) µm] of M-Porous group (P < 0.05). The surface of 3D-Porous group appeared with more regular round pores than that of M-Porous group. The contact angles of all the groups were less than 90°. The contact angles of 3D-Ctrl (73.83°±5.34°) and M-Porous group (72.7°±2.72°) were the largest, with no significant difference between them (P>0.05). Cells adhered inside the pores in M-Porous and 3D-Porous groups, and the proliferation activities of them were significantly higher than those of M-Ctrl and 3D-Ctrl groups after 3 and 5 days' culture (P < 0.05). After 14 days' incubation, ALP, Colla1, Runx2 and OCN mRNA expression in 3D-Porous groups were significantly lower than those of M-Ctrl and 3D-Ctrl groups (P < 0.05). Colla1, Runx2 and OCN mRNA expressions in M-Porous group were higher than those of 3D-Porous group (P < 0.05). CONCLUSION: The porous surface morphology of zirconia can promote the proliferation and adhesion but inhibit the differentiation of MC3T3-E1 cells.

[Reality and expectation of machine learning in critically ill patients with acute kidney injury].

The prediction model constructed by machine learning can early predict acute kidney injury (AKI) in critically ill patients, which contributes to taking preventive measures to reduce incidence of AKI as soon as possible. Machine learning can also identify AKI subtypes in real time, so as to facilitate the implementation of precise treatments for their subtypes in the future, which may improve the prognosis of patients. In this article, the construction of forecasting model of AKI and identification of AKI subtypes in critically ill patients and it's precise treatment with machine learning, limitations and development trend of machine learning in the field of AKI in critically ill patients is addressed for clinical reference.

[Familial interstitial lung disease associated with surfactant protein C gene mutation in adults: report of two cases and literature review].

Objective: To improve the understanding of clinical manifestations, imaging findings, diagnosis and treatment of surfactant protein C gene (SFTPC) mutation associated with familial interstitial lung disease in adults. Methods: Two cases of adult SFTPC gene mutation associated with familial interstitial lung disease diagnosed in the Affiliated Hospital of Medical School of Ningbo University were analyzed retrospectively, and the literature was reviewed. The literatures were retrieved with "family interstitial lung disease" "SFTPC gene" "surface protein C gene" "SFTPC gene mutation associated with familial international lung disease" and "surface protein C gene mutation associated with familial international lung disease" in PubMed, Embase, Ovid, Wanfang database and China National Knowledge Infrastructure (CNKI). Results: There were two patients with familial interstitial lung diseases(one male and one female) with an average age of 27.5 years. Ⅱ-2 patient had symptoms of dry cough and shortness of breath, and Ⅱ-1 patient had no symptoms. There were multiple cysts and fine reticular shadows in both cases. Ⅱ-2 patient had multiple ground glass opacities in both lower lungs. TheⅡ-2 patient was diagnosed with usual interstitial pneumonia (UIP) by transbronchial lung cryobiopsy. A total of 35 patients were included in this literature review, including 20 males, with an average age of 33.5 years. Of all the patients, the clinical symptoms were described in 30 patients. The main manifestations were shortness of breath (22/30), dry cough (18/30), clubbing finger (12/30), and 30% (9/30) of them were found by chest computerized tomography (CT) without symptoms. There were 17 cases with detailed description of chest CT imaging. The most common chest CT findings were multiple intralobular reticular opacities (17/17), multiple cysts (12/17) and ground glass opacities (7/17). The main histopathological pattern was UIP (24/26). Conclusions: The main clinical manifestations of SFTPC gene mutation associated with familial interstitial lung disease in adults are shortness of breath, dry cough and clubbing fingers. The main manifestations are multiple cysts and intralobular reticular opacities in combination with multiple ground glass opacities. There is no specific drug in the treatment at present and early treatment with hydroxychloroquine may have better curative effect. When the imaging findings show multiple cysts and intralobular reticular opacities in combination with multiple ground glass opacities, especially the age of onset is less than 50 years old, this disease should be considered.

[Clinical features and survival analysis of microscopic polyangiitis-associated interstitial lung disease:a retrospective study of 28 patients].

Objective: To explore the clinical features, laboratory examination and imaging features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD), and to perform survival analysis. Methods: The records of 28 patients with MPA-ILD who were treated at the Affiliated Hospital of Medical School of Ningbo University were reviewed retrospectively from August 2014 to November 2021. The patients' clinical features, laboratory parameters, pulmonary function test, echocardiography, chest CT scan findings and therapeutic regimen were analyzed, and the relevant data were statistically analyzed. Results: There were 18 males and 10 females, with an average age of (70.1±9.3) years. Among them, 13 patients had a history of smoking. The main clinical manifestations were cough (14/28), fever (12/28), chest tightness, shortness of breath (12/28) and hemoptysis (3/28). Sixteen patients had renal involvement, and 78.57% (22/28) and 89.28% (25/28) of the patients had elevated C-reactive protein (CRP) and ESR respectively. Sixteen (16/28) patients had increased rheumatoid factor (RF), and the positive rate of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) was 82.12% (23/28). 96.43% (27/28) of ILDs were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly usual interstitial pneumonia (UIP) or UIP-like (15/28), followed by nonspecific interstitial pneumonia (NSIP) (8/28). Compared with non-UIP-like patients, UIP or UIP-like patients were older (P=0.018), and had higher serum LDH level (P=0.041), but serum creatinine level was significantly lower (P=0.041). Univariate and multivariate survival analysis showed that inappropriate treatment (HR=9.81, 95%CI: 1.68-57.29, P=0.011) and elevated serum LDH (HR=4.11, 95%CI: 0.99-17.00, P=0.051) were independent risk factors for shortened survival of MPA-ILD, while elevated RF (HR=0.22, 95%CI: 0.06-0.91, P=0.037) was a protective factor for prolonged survival. Conclusions: MPA-ILD patients had fewer systemic vasculitis symptoms. Most of the ILD patients were diagnosed before or at the same time as MPA. The chest radiological pattern was mainly UIP or UIP-like, followed by NSIP. Early use of glucocorticoids combined with immunosuppressant or rituximab could improve the survival rate of MPA-ILD. The elevated serum LDH was an independent risk factor for shortened survival of MPA-ILD, while elevated RF was a protective factor for prolonged survival.

CircRNA_103801 accelerates proliferation of osteosarcoma cells by sponging miR-338-3p and regulating HIF-1/Rap1/PI3K-Akt pathway.

This study aimed to investigate the roles of hsa_circRNA_103801 in the progression of osteosarcoma (OS) cells. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the expression level of circRNA_103801 in OS cells. Cell count kit-8 and Transwell migration and invasion assays were employed to detect the proliferation, migration, and invasion abilities of OS cells. The effects of circRNA_103801 on the apoptosis of OS cells were identified by flow cytometry. The binding relationship between circRNA_103801 and miR-338-3p was verified by bioinformatics analysis. MiR-338-3p level in OS cell lines was detected by RT-qPCR. Additionally, Western blotting was utilized to detect the expression levels of HIF-1, Rap1, PI3K, and Akt in OS cells. The results showed that the expression level of circRNA_103801 was significantly up-regulated in OS patients' tissues. Inhibiting the expression level of circRNA_103801 could attenuate the proliferation, migration, and invasion abilities of OS cells. In addition, the down-regulated expression level of circRNA_103801 could induce cell apoptosis. The results of the luciferase reporter assay suggested that circRNA_103801 could be combined with miR-338-3p, and the RT-qPCR revealed that the miR-338-3p level in OS cells after knockdown of circRNA_103801 was elevated compared with the control group. The results of Western blotting suggested that the expression levels of HIF-1, Rap1, PI3K, and Akt were elevated in OS cells. In conclusion, the circRNA_103801-miR-3388-3p-HIF-1/Rap1/PI3K-Akt pathway could be a therapeutic target of OS.

[Protein Disulfide Bonds Detected by Tagging with High Molecular Weight Maleimide Derivative].

Disulfide bridges are essential for maintaining the structure and function of proteins. Traditionally, studies of the disulfide bonds require expensive equipment and high purity of the protein sample, therefore, the development of simpler techniques is warranted. Here, were present a novel protocol for the detection of disulfide bonds in proteins, which is based on the labeling reduced disulfide bridges with a high molecular weight (HMW) maleimide derivative. After irreversible blocking of free thiol groups of proteins, the labeling of new thiols released from disulfide bridges with a high-molecular-weight (HMW) maleimide derivative is performed. To confirm localization of cysteines involved in the formation of disulfide bonds, cysteine mutagenesis was conducted. For validation, aquaporin 5 (AQP5) and transient receptor potential cation channel subfamily V member 4 (TRPV4) proteins were tagged with FLAG (DYKDDDDK) on N-termini. Increase in MW of the target proteins from immunoblot indicated the presence of disulfide bonds. No bands with increased MW were detected in AQP5, while TPRV4 cysteines at disulfide bridges-constituting positions 639, 645, 652, 660, 770 were detected and confirmed by cysteine mutagenesis. These data indicate that the proposed technique is feasible and effective for the detection of protein disulfide bonds.

[Effects of femtosecond laser treatment on surface characteristics and flexural strength of zirconia].

OBJECTIVE: To evaluate the effects of femtosecond laser treated microgrooved surface on microscopic topography, phase transformation, and three-points flexural strength of zirconia, and to provide reference for surface microstructure optimization of zirconia implant. METHODS: According to different surface treatment methods, 57 computer aided design/computer aided manufacture (CAD/CAM) zirconia bars (20.0 mm×4.0 mm×1.4 mm) were evenly divided into three groups: sintered group, no treatment after sintering, taken as control; sandblasted group, sandblasted with 110 µm aluminium oxide (Al2O3) after sintering; microgrooved group, femtosecond laser fabricated microgrooves with 50 µm width, 30 µm depth, and 100 µm pitch. Surface microscopic topography was observed with scanning electron microscope (SEM) and 3D laser microscope. Further, surface roughness in each group and microgroove size were measured. Crystal phase was analyzed with X-ray diffraction. Specimens were subjected to three- points flexural strength test, and Weibull distribution was used to analyze their strength characteristics. RESULTS: SEM showed that sintered surface was flat with clear grain structure; sandblasted surface exihibited bumps and holes with sharp margins and irregular shape; microgrooves were regularly aligned without evident defect, and nano-scale particles were observed on the surface inside of the microgrooves. Ra value of microgrooved group [(9.42±0.28)] µm was significantly higher than that of sandblasted group [(1.04±0.03) µm] and sintered group [(0.60±0.04) µm], and there was statistical difference between sandblasted group and sintered group (P < 0.001). The microgroove size was precise with (49.75±1.24) µm width, (30.85±1.02) µm depth, and (100.58±1.94) µm pitch. Crystal phase analysis showed that monoclinic volume fraction of sandblasted group (18.17%) was much higher than that of sintered group (1.55%), while microgrooved group (2.21%) was similar with sintered group. The flexural strength of sandblasted group (986.22±163.25) MPa had no statistical difference with that of sintered group (946.46±134.15) MPa (P=0.847), but the strength in microgrooved group (547.92±30.89) MPa dropped significantly compared with the other two groups (P < 0.001). Weibull modulus of sintered, sandblasted, microgrooved groups were 7.89, 6.98, and 23.46, respectively. CONCLUSION: Femtosecond laser was able to form micro/nanostructured microgrooves on zirconia surface, which deleteriously affected the flexural strength of zirconia.

[Quantitative analysis of occlusal changes in posterior partial fixed implant supported prostheses].

OBJECTIVE: To analyze changes in occlusal force distribution and occlusal contact in posterior partial fixed implant-supported prostheses over time, and to provide reference for the precise occlusion design, adjustment and maintenance of implant prostheses. METHODS: According to certain inclusion and exclusion criteria, patients were recruited from partially edentulous patients who had received implant-supported single crown or fixed bridge in the posterior region. The patients were collected since the implant prostheses settling and scheduled for the routine examination of implant prostheses and the occlusal examinations of complete dentition after 2 weeks, 3, 6, and 12 months. Occlusal examinations were taken with the articulating papers and T-Scan III (Tekscan, South Boston, USA), which could check and measure the occlusal contact condition of complete dentition. The occlusion time and relative occlusal forces of implant prostheses, mesial adjacent teeth and control teeth were recorded at the same time. RESULTS: Thirty-seven posterior partial fixed implant prostheses in 33 patients (17 women and 16 men, aged 24-70 years) were followed up for 3-12 months (average 8.3 months). At baseline, the relative occlusal forces of implant prostheses were significantly lower than those of the corresponding control teeth (P<0.001). However, after 3 months, the relative occlusal forces of implant prostheses had significantly increased (P<0.05), while control teeth decreased significantly (P<0.05), resulting in no statistical significance between them. The implant prostheses occlusion time ratio also increased significantly from 2 weeks to 3 months (P<0.05). There was no significant difference from the third month to the sixth month, or from the sixth month to the twelfth month (P>0.05). CONCLUSION: Light contact and time-delayed occlusion of posterior implant prostheses changes significantly in the first three months after settling implant prostheses. These changes mainly include the advance of the time point of the implant prosthesis to start the occlusion contact, and the increase of the occlusal force of the implant prosthesis. The occlusion of posterior implant prostheses should be carefully monitored at end of the third month follow-up clinically.

[A functional magnetic resonance imaging study of exercise addiction].

Objective: To investigate the brain activities of exercise addiction (EA) group people with the task-functional magnetic resonance image (task-fMRI). Methods: A total of 29 exercise addicts (addiction group, average age 46±4 years) and 26 non-exercise addicts (control group, average age 46±6 years) matched by sex, age, average education level and sports dependence degree were selected by using exercise addiction index (EAI) through questionnaires to members of Jiangsu Local Fitness and Long-distance Running Association between January 2018 and June 2018. The participants were scanned with fMRI while watching sports pictures or non-sports pictures. The brain responses of the two groups under two stimulation tasks were analyzed and compared. Results: Compared with the control group, while watching sports pictures, the right fusiform gyrus (MNI:x=30, y=-87, z=0), left posterior central gyrus (MNI:x=-51, y=-21, z=54), left medial superior frontal gyrus (MNI:x=-9, y=54, z=30), and right middle occipital gyrus (MNI:x=42, y=-72, z=36) were significantly inhibited in the addiction group (t-test, all P<0.05). When watching non-sports pictures, the addictive group showed the left superior frontal gyrus (MNI:x=-12, y=54, z=30), left middle frontal gyrus (MNI:x=-30, y=18, z=45), right inferior frontal gyrus (MNI:x=42, y=33, z=-12), right occipital gyrus (MNI:x=42, y=-72, z=36), and they were more significantly inhibited than the control group (t-test, all P<0.05). Conclusion: Compared to the control group, the EA group shows significant brain inhibition with visual stimulation, particularly with non-sports pictures.

Hedgehog Spin-Vortex Crystal Antiferromagnetic Quantum Criticality in CaK(Fe_{1-x}Ni_{x})_{4}As_{4} Revealed by NMR.

Two ordering states, antiferromagnetism and nematicity, have been observed in most iron-based superconductors (SCs). In contrast to those SCs, the newly discovered SC CaK(Fe_{1-x}Ni_{x})_{4}As_{4} exhibits an antiferromagnetic (AFM) state, called hedgehog spin-vortex crystal (SVC) structure, without nematic order, providing the opportunity for the investigation into the relationship between spin fluctuations and SC without any effects of nematic fluctuations. Our ^{75}As nuclear magnetic resonance studies on CaK(Fe_{1-x}Ni_{x})_{4}As_{4} (0≤x≤0.049) revealed that CaKFe_{4}As_{4} is located close to a hidden hedgehog SVC AFM quantum-critical point (QCP). The magnetic QCP without nematicity in CaK(Fe_{1-x}Ni_{x})_{4}As_{4} highlights the close connection of spin fluctuations and superconductivity in iron-based SCs. The advantage of stoichiometric composition also makes CaKFe_{4}As_{4} an ideal platform for further detailed investigation of the relationship between magnetic QCP and superconductivity in iron-based SCs without disorder effects.

Spectrum and origin of mutations in sporadic cases of haemophilia A in China.

INTRODUCTION: About 30% of haemophilia A (HA) patients are sporadic cases. It is important to confirm the mutation origin and carrier status in these families. AIM: To describe the spectrum and origin of the mutations in 393 Chinese sporadic HA families and identify potential mosaics among non-carrier mothers. METHODS: AccuCopy quantification combined with long-distance PCR was used for genotyping intron 22/1 inversion (Inv22/Inv1) and Inv22 mosaicism. F8 gene sequences were analysed by direct sequencing. Copy number variations of F8 gene were detected by AccuCopy method. Six short tandem repeats related to F8 gene were applied for linkage analysis. Mosaicism of point mutations/small deletions/insertions was determined by ddNTP primer extension method. RESULTS: Most of sporadic patients' mothers are carriers, in 257 cases with integral family members, 60% have the mutations tracing back to their fathers, 12% to their mothers. 28% had de novo mutations with non-carrier mothers as revealed by routine genetic studies. Mutation spectrum of sporadic families was different in groups with different origins of mutations. Point mutation (51%) was the predominant mutation type in pedigrees with de novo mutations. While, in families with mutations inherited from maternal grandfathers, Inv22 was the main type (51%). We found somatic mosaic in mothers of 30% (3/10) pedigrees with de novo Inv22 and 11.5% (3/26) pedigrees with point mutations. CONCLUSION: The spectrum of F8 genetic variants identified in sporadic families was fairly diverse. The high prevalence of chimaeras in carriers suggests that more cautions should be taken in genetic counselling of sporadic haemophilia families.

[Relationship between expression of RBM38 and distant metastasis and prognosis of breast cancer].

Objective: To investigate the relationship between the expression of RNA-binding protein 38 (RBM38) and distant metastasis and prognosis of breast cancer. Methods: A total of 161 cases of breast cancer tissues were selected, and the expression of RBM38 was detected by immunohistochemical SP method. The relationship between the expression of RBM38 and the distant metastasis and prognosis of breast cancer patients were analyzed. Cox regression model was applied to analyze the influence factors of distant metastasis of breast cancer. Results: Among the 161 breast cancer patients, high expression of RBM38 was observed in 85 cases and low expression was observed in 76 cases. Log rank test showed that the distant metastasis rate of RBM38 highly expressed group was significantly lower than that of RBM38 lowly expressed group (P=0.010), while the survival rate was significantly higher (P=0.009). Univariate Cox regression analysis showed that the pathological stage (P=0.001), axillary lymph node positive (P=0.001), and the expression of RBM38 (P=0.015) were dramatically related to the distant metastasis of breast cancer patients. Multivariate Cox regression analysis showed that positive axillary lymph node was an independent risk factor (RR=4.222, 95% CI: 1.235-14.432), and high expression of RBM38 was an independent protective factor (RR=0.328, 95% CI: 0.128-0.839) of distant metastasis of breast cancer patients. Conclusion: High expression of RBM38 is positively related with low distant metastasis rate and good prognosis of breast cancer patients. Hence, high expression of RBM38 is an independent protective factor of distant metastasis.