[ANCA-negative granulomatosis with polyangiitis: a case report].

We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.

[Research on friction and wear behaviors of silicon-lithium spray coating on zirconia ceramics].

OBJECTIVE: To study microstructure, friction and wear behaviors of silicon-lithium spray coating on the surface of zirconia ceramics and to preliminarily evaluate its esthetic so as to provide support and guidance for the clinical application. METHODS: Zirconia ceramic specimens were randomly divided into three groups: coating group (two subgroups), polishing group (two subgroups), and glazing group (four subgroups), with 10 samples in each subgroup. The two subgroups of coating group were the zirconia ceramics with the untreated and preliminary polishing surfaces sprayed with silicon-lithium coating, respectively. The two subgroups of polishing group were preliminary polishing and fine polishing of zirconia ceramics, respectively. The four subgroups of glazing group were preliminarily polished zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively; and untreated zirconia ceramics glazed with Biomic and Stain/Glaze products, respectively. The above 8 subgroups of zirconia ceramic specimens were used as friction pairs with 80 steatite ceramics for 50 000 chewing cycles under 50 N vertical load and artificial saliva lubrication using chewing simulation. Scanning electron microscope was used to observe the microstructure of the surface and section of the coating group, and the thickness of the coating and glazing were measured. The linear roughness of the coating and polishing groups was mea-sured using a laser confocal scanning microscope. Vickers hardness was measured using a microhardness tester and the esthetic of zirconia ceramic full crown sprayed with silicon-lithium coating was preliminarily evaluated. White light interferometer was used to measure the width, the maximum depth and the volume of the wear scars of each group, and the wear depth of steatite ceramics and wear rate of zirconia ceramic specimens were calculated. Kruskal-Wallis nonparametric test and Dunn's multiple comparisons test were used to analyze the wear depth of each group (α=0.05). RESULTS: The microstructures of the silica-lithium spray coatings on the untreated and preliminarily polished zirconia ceramic surfaces showed the protruding defects, and the line roughness of coating group was larger than that of the polishing group. The median thickness of the silica-lithium spray coating on the preliminarily polished zirconia ceramic was 13.0 µm (interquartile range, IQR: 11.6, 17.9), while that of the silica-lithium spray coating on the untreated zirconia ceramic was 4.4 µm (IQR: 4.1, 4.7). The Vickers hardness and wear rate of the coating group were between the polishing group and the glazing group. The wear depths of the wear scars of steatite ceramics were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference between glazing and polishing groups (P < 0.05). With the increase of polishing procedure, the wear depth of steatite ceramics decreased in each subgroups. The orders of maximum depth and volume of wear scars of zirconia ceramic were the glazing group, coating group, and polishing group in descending order, and there was statistically significant difference in the maximum depth of wear scars between glazing and polishing groups (P < 0.05). CONCLUSION: The silica-lithium spray coating on the zirconia ceramic, can be used as a new method for zirconia ceramic surface treatment, because it can increase the esthetic of zirconia ceramics compared with polishing and reduce the wear of steatite ceramics compared with glazing.

[Independent innovation research, development and transformation of precise bionic repair technology for oral prosthesis].

According to the fourth national oral health epidemiological survey report (2018), billions of teeth are lost or missing in China, inducing chewing dysfunction, which is necessary to build physiological function using restorations. Digital technology improves the efficiency and accuracy of oral restoration, with the application of three-dimensional scans, computer-aided design (CAD), computer-aided manufacturing (CAM), bionic material design and so on. However, the basic research and product development of digital technology in China lack international competitiveness, with related products basically relying on imports, including denture 3D design software, 3D oral printers, and digitally processed materials. To overcome these difficulties, from 2001, Yuchun Sun's team, from Peking University School and Hospital of Stomatology, developed a series of studies in artificial intelligence design and precision bionics manufacturing of complex oral prostheses. The research included artificial intelligence design technology for complex oral prostheses, 3D printing systems for oral medicine, biomimetic laminated zirconia materials and innovative application of digital prosthetics in clinical practice. The research from 2001 to 2007 was completed under the guidance of Prof. Peijun Lv and Prof. Yong Wang. Under the support of the National Natural Science Foundation of China, the National Science and Technology Support Program, National High-Tech R & D Program (863 Program) and Beijing Training Project for the Leading Talents in S & T, Yuchun Sun's team published over 200 papers in the relevant field, authorized 49 national invention patents and 1 U.S. invention patent and issued 2 national standards. It also developed 8 kinds of core technology products in digital oral prostheses and 3 kinds of clinical diagnosis and treatment programs, which significantly improved the design efficiency of complex oral prostheses, the fabrication accuracy of metal prostheses and the bionic performance of ceramic materials. Compared with similar international technologies, the program doubled the efficiency of bionic design and manufacturing accuracy and reduced the difficulty of diagnosis and cost of treatment and application by 50%, with the key indicators of those products reaching the international leading level. This program not only helped to realize precision, intelligence and efficiency during prostheses but also provided functional and aesthetic matches for patients after prostheses. The program was rewarded with the First Technical Innovation Prize of the Beijing Science and Technology Awards (2020), Gold Medal of Medical Research Group in the First Medical Science and Technology Innovation Competition of National Health Commission of the People's Republic of China (2020) and Best Creative Award in the First Translational Medical Innovation Competition of Capital (2017). This paper is a review of the current situation of artificial intelligence design and precision bionics manufacturing of complex oral prosthesis.

[Finite element analyses of retention of removable partial denture circumferential clasps manufactured by selective laser melting].

OBJECTIVE: To compare the retentions of different designs of cobalt-chromium (Co-Cr), pure titanium (CP Ti), and titanium alloy (Ti-6Al-4V) removable partial denture (RPD) circumferential clasps manufactured by selective laser melting (SLM) and to analyze the stress distribution of these clasps during the removal from abutment teeth. METHODS: Clasps with clasp arm size A (1.9 mm width/1.1 mm thickness at the body and 0.8-taper) or B (1.2 times A) and 0.25 mm or 0.50 mm undercut engagement were modeled on a prepared first premolar die, named as designs A1, A2, A3, and A4, respectively. The density and elastic modulus of SLM-built Co-Cr, CP Ti, and Ti-6Al-4V were measured and given to different groups of clasps. The density, elastic modulus, and Poisson ' s ratio of enamel were given to the die. The control group was the cast Co-Cr clasp with design A1, to which the density and elastic modulus of cast Co-Cr alloy were given. The Poisson's ratio of all metals was 0.33. The initial 5 N dislodging force was applied, and the maximum displacement of the clasp along the insertion path was computed. The load was reapplied with an increment of 5 N than in the last simulation until the clasp was completely dislodged. The retentive force range of different groups of clasps was obtained. The retentive forces of the SLM-built Co-Cr, CP Ti, and Ti-6Al-4V clasps with equivalent computed retentive force range to the control group were validated through the insertion/removal experiment. The von Mises stress distributions of these three groups of SLM-built clasps under 15 N loads were analyzed. RESULTS: SLM-built Co-Cr, CP Ti, and Ti-6Al-4V clasps with designs B1 or B2, and Co-Cr clasps with design A2 had higher retentive forces than those of the control group. SLM-built CP Ti and Ti-6Al-4V clasps with design A1 had lower retentive forces than those of the control group. SLM-built Co-Cr clasp with design A1 and SLM-built CP Ti and Ti-6Al-4V clasps with design A2 had equivalent retentive forces to those of the control group. The insertion/removal experiment showed that the measured retentive forces of these three groups of SLM-built clasps were (21.57±5.41) N, (19.75±4.47) N, and (19.32±2.04) N, respectively. No statistically significant measured retentive force difference was found among these three groups of SLM-built clasps (P>0.05). The maximum von Mises stress of these three groups of SLM-built clasps exceeded their responding yield strength except for the Ti-6Al-4V one. CONCLUSION: SLM-built Co-Cr circumferential clasps had higher retention than CP Ti and Ti-6Al-4V ones with the same clasp arm size and undercut engagement. The retention of SLM-built circumferential clasps could be adjusted by changing the undercut engagement and clasp arm size. If SLM-built circumferential clasps are used in clinical practice, the Ti-6Al-4V clasp with clasp arm size A and 0.50 mm undercut engagement is recommended considering the long-term use of RPD in the patient's mouth.

[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.

[Hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis: A case report].

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.

[Significance of aspergillus fumigatus-specific IgG in the diagnosis of allergic bronchopulmonary aspergillosis].

The data of 18 patients with allergic bronchopulmonary aspergillosis (ABPA) who received aspergillus fumigatus-specific IgG detection from 2015 to 2021 in Peking University Third Hospital were retrospectively analyzed. Among them, 11 were male and 7 were female, aged 18-79 years. All patients had a history of asthma or symptoms of cough and asthma, and aspergillus fumigatus-specific IgE was positive; 16 patients had total serum IgE>500 U/ml, of which 13 patients had total serum IgE>1 000 U/ml. Among other diagnostic indicators, peripheral blood eosinophils were >0.5×109/L in 16 cases; lung CT showed bronchiectasis in 15 cases; serum aspergillus fumigatus-specific IgG was positive (>120 AU/ml) in 10 cases. There was no significant difference in serum total IgE level, peripheral blood eosinophil count, and bronchiectasis ratio between positive and negative cases of aspergillus fumigatus-specific IgG (all P>0.05). In this study, the positive rate of aspergillus fumigatus-specific IgG in patients with ABPA was more than 50%, which has auxiliary value in the diagnosis of ABPA.

[Focus on influenza vaccination in patients with chronic obstructive pulmonary disease].

Influenza vaccination has been shown to reduce lower airway infections requiring hospitalization, and reduce mortality and exacerbation frequency in patients with chronic obstructive pulmonary disease(COPD), and therefore is recommended for all COPD patients by guidelines. However, the coverage of influenza vaccination in Chinese COPD patients is far from satisfactory. The large-scale COVID-19 vaccination may have a positive impact on the attitude towards influenza vaccines, and healthcare professionals should take active measures to improve the rate of influenza vaccination in patients with COPD.

[Nutrition management of patients with acute exacerbation of chronic obstructive pulmonary disease hospitalized in Respiratory Intensive Care Unit].

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is an important part of the course of COPD. Patients with life-threatening acute exacerbation need to be admitted to the respiratory intensive care unit (RICU) for treatment in time. Malnutrition is common in COPD patients, and nutritional risk also has a high prevalence in patients with COPD exacerbation, which is closely associated with the clinical outcome and mortality of these patients. Identifying patients with high nutritional risk and providing appropriate nutritional treatment will help to improve survival rate, shorten length of hospital stay and reduce complications. This review describes the potential mechanisms of malnutrition in patients with COPD, the nutritional risk assessment of patients with COPD exacerbation hospitalized in RICU, the selection of nutritional treatment methods and formulas, and the relevant problems of nutritional management of patients required noninvasive ventilation, hoping to provide information for the optimization of nutritional treatment strategy for acute exacerbation of COPD and the exploration of clinical research in the future.

[A survey on the application of diagnostic and evaluation tools for chronic obstructive pulmonary disease among respiratory physicians].

Objective: To investigate the current status of the application of diagnostic and assessment tools for chronic obstructive pulmonary disease(COPD) by respiratory physicians in China. Method: An on-line questionnaire was designed to address the common questions in COPD diagnosis and evaluation, and this survey was conducted through Wechat. Result: A total of 3 204 valid questionnaires were collected. 71.7% of the physicians were from tertiary hospitals. 75.4% of the physicians diagnosed COPD strictly on the basis of lung function results after inhaled bronchodilators, and this percentage was higher in tertiary hospitals than in secondary hospitals(78.71% vs. 66.92%, P<0.01). 99.3% of the physicians evaluated symptoms of dyspnea, but 26.8% of physicians did not use a scoring system(CAT or mMRC) for quantitative assessment. Although 83.8% of physicians would use the guideline-recommended comprehensive assessment(ABCD classification), only 45.1% of them chose initial therapy exactly according to the classification. In addition, 28.3% of physicians did not routinely order blood eosinophil counts and 20.1% did not inquire the history of tuberculosis. Conclusions: Although most respiratory physicians followed the guidelines in the diagnosis and evaluation of COPD, the use of assessment tools was inadequate, which should be addressed in educational programs for COPD management.

[Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology].

Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

[Evaluation of fracture strength of two kinds of zirconia all-ceramic crowns with different edge compensation angles].

OBJECTIVE: To evaluate the effects of different edge compensation angles on the fracture strength of multilayer zirconia all-ceramic crowns and traditional uniform zirconia all-ceramic crowns. METHODS: The resin tooth preparation specimen of the mandibular first molar with a knife-edge was fabricated. A 3D digital model of the specimen was obtained by scanning it with a 3D dental model scanner. The 3D digital model was imported into computer aided design (CAD) software, and three 3D digital models of the full crown with the same surface shape are designed with the edge compensation angles of 30°, 45° and 60°, respectively. Then, the designed 3D digital model is imported into computer aided manufacturing (CAM) software. Three kinds of multilayer and homogeneous zirconia all-porcelain crowns with different edge compensation angles were fabricated, 10 each for a total of 60. The fracture load of each crown was measured under the electronic universal testing machine. RESULTS: Fracture load of multilayer and uniform zirconia all-ceramic crowns, (4 322.86±610.07) N and (5 914.12±596.80) N in the 30° group, (5 264.82±883.76) N and (5 220.83±563.38) N in the 45° group and (4 900.42±345.41) N and (5 050.22±560.24) N in the 60° group, respectively. The fracture load of multi-layer zirconia all-ceramic crowns in the 30° group was significantly lower than that of homogeneous zirconia all-ceramic crowns(P < 0.05); there was no statistical significance in 45° group and 60° group(P>0.05). In the multi-layer zirconia all-ceramic crowns: the fracture load of the 30° group was significantly lower than that of the 45° group (P < 0.05); there was no significant difference between the 30° group and the 60° group, the 45° group and the 60° group (P>0.05).In uniform zirconia full crown group: the 30° group was higher than the 45° group, the 30° group was higher than the 60° group (P < 0.05), and there was no significant difference between the 45° group and the 60° group (P>0.05). CONCLUSION: The fracture loads of three kinds of uniform and multilayer zirconia all ceramic crowns with different edge compensation angles can meet the clinical requirements. A smaller edge compensation angle is recommended when using traditional zirconia all-ceramic crowns, while 45° is recommended when using multi-layer zirconia all-ceramic crowns.

[Evaluation of methods for fitness of removable partial denture].

OBJECTIVE: To compare the differences and indications of three evaluation methods for fitness evaluation of removable partial denture (RPD). METHODS: A RPD was fabricated and seated on the stone cast of a partially edentulous mandible, and the spaces between RPD and stone cast were recorded with polyvinyl siloxane (PVS) impression material forming PVS replicas. Using cross sectional measurement, the average thicknesses of PVS replicas were measured under stereomicroscope with different numbers of selected measuring points in the denture base, major connector, occlusal rest of the RPD, and the average thicknesses of the PVS replicas measured with different numbers of measuring points were compared using one-way analysis of variance (ANOVA) and independent sample t test. Three kinds of method, including cross sectional measurement, three-dimensional analysis on the stone cast, and three-dimensional analysis on the polyether cast, were applied to measure the average thicknesses of the PVS replicas, and the average thicknesses of the PVS replicas measured by these three evaluation methods were compared with ANOVA. RESULTS: For cross sectional measurement, statistically significant differences were found in the average thicknesses of the PVS replicas in the denture base and the major connector among the different numbers of measuring points (P < 0.05), but no differences were found in the average thicknesses of the PVS replicas in the occlusal rest (P>0.05). There were significant differences among the average thicknesses of the PVS replicas measured by these three evaluation methods in each component of the RPD (P < 0.01). The average thickness measured by three-dimensional analysis on the stone cast and three-dimensional analysis on polyether cast were smaller than that measured by cross sectional measurement (P < 0.05). And there were no differences between the average thicknesses of PVS replicas measured by three-dimensional analysis on stone cast and three-dimensional analysis on polyether cast (P>0.05). CONCLUSION: For cross sectional measurement, the average thickness of the PVS replicas was influenced by the number of measuring points, and the measurement accuracy of cross sectional measurement was not reliable enough. Three-dimensional analysis on stone cast which is suitable for evaluation in vitro and three-dimensional analysis on polyether cast which is suitable for evaluation in vivo can evaluate the fitness of RPD more comprehensively and effectively than that of cross sectional measurement.

[Analysis of PARP inhibitors induced anemia in advanced and relapsed epithelial ovarian cancer].

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

[Preliminary study on three digital analysis methods for analyzing the distribution and area of occlusal contacts].

OBJECTIVE: To analyze the distribution and area of occlusal contacts of clinical dental model using three kinds of digital analysis methods, to compare the results of these methods and traditional occlusal analysis method, and to further analyze the characteristics of each digital analysis method. METHODS: A set of plaster models of normal subjects was selected. The models were scanned by lab scanner 3shape E4 and the files were exported in a stereolithography file format. In 3D analysis software Geomagic Studio 2013 and Geomagic Qualify 2013, the corresponding results of 3D occlusal contact distribution and occlusal contact area were obtained through three digital analysis methods: "3D color difference map method", "point cloud analysis method", and "virtual articulating paper method". The occlusal contact distribution and occlusal contact area were also obtained by two traditional occlusal analysis methods: "silicone interocclusal recording material method" and "scanned articulating paper mark method". A threshold of 100 µm was used to analyze the occlusal contacts and 100 µm was also the thickness of articulating paper used in this study. The results of these five different occlusal analysis methods were evaluated qualitatively and quantitatively. RESULTS: The results of 3D occlusal contact distribution obtained by the above five methods were basically consistent. The total occlusal contact area obtained by 3D color difference map method, point cloud analysis method, virtual articulating paper method, silicone interocclusal recording material method and scanned articulating paper mark method were 133.10 mm², 142.08 mm², 128.95 mm², 163.31 mm², and 100.55 mm² respectively. There was little difference between the results of three digital analysis methods. The results of occlusal contact area obtained by the digital methods and the traditional methods were different. CONCLUSION: The three digital analysis methods can provide reliable and accurate analysis results of occlusal contact distribution and occlusal contact area of dental model. The results obtained by these methods can serve as references for the digital occlusal surface design of dental prosthesis and clinical occlusal analysis.

[Evaluation of clinical efficacy of a kind of digital complete denture].

OBJECTIVE: To compare the clinical efficacy of a kind of complete dentures fabricated using computer aided design/computer aided manufacturing (CAD/CAM) workflow with that of the complete denture fabricated using conventional workflow. METHODS: Twenty edentulous patients were included in this prospective, single-blind, self-controlled clinical trial. Two pairs of complete dentures were fabricated for each participant: one using the functional suitable denture (FSD) system with CAD/CAM, and the other using conventional fabrication workflow. In the final delivery appointment, the conventional dentures worn by the participant for 3 months at first. Then the participant swapped to wear digital denture for another 3 months. The patients' satisfaction and oral health related quality of life (OHRQoL) were measured using the visual analogue scale (VAS) and oral health impact profile (OHIP-20E) at baseline, 2 weeks, 1 month, 2 months, and 3 months following denture delivery. In addition, the masticatory efficiency of each pair of dentures was measured after three months adaptation period for each type of dentures. RESULTS: The VAS scores of the twenty patients in FSD denture group on general satisfaction, ease of cleaning, ability to speak, esthetics, stability and oral health status on these six domains were higher than that of conventional denture group 3 months after delivery. While the VAS cores in FSD denture group on comfort, ability to chew and ability to chew up were the same as those of conventional denture group. But there was no significant difference (P>0.05). The VAS score on each domain in FSD denture group was higher than that of conventional denture group 3 months after delivery, three domains of which reached statistical significance (P < 0.05), involving functional limitation, psychological discomfort and total. The masticatory performance of the FSD denture (1.20±0.54) was slightly higher than that for the conventional denture (1.16±0.53), but the difference did not reach statistical significance (P=0.691). CONCLUSIONS: The clinical efficacy of the FSD complete denture is comparable to that of the conventional complete denture. As for patient satisfaction and oral health related quality of life, FSD dentures received comparable scores as conventional complete dentures did.

[Method and accuracy of determining the jaw position of repositioning splint with the aid of digital technique].

OBJECTIVE: To establish the workflow of determining the jaw position of repositioning splint with the aid of digital technique, and to evaluate the accuracy of this workflow and compare the accuracy of raising different vertical dimensions in vitro. METHODS: A volunteer was recruited. The data of full-arch scans, cone beam computed tomography (CBCT) image and ultrasonic jaw motion tracking of the volunteer were acquired. The full-arch scans were merged with the CBCT image, which were then matched to the jaw motion tracking reference system. The jaw position of repositioning splint was determined when the anterior teeth opening was 3 mm and the condyle was in centric relation of the fossa in the sagittal plane. A digital repositioning splint was designed in the software based on virtual articulator and fabricated with additive manufacturing technique. After the splint was tried in, another CBCT image was taken and a qualitative analysis was conducted to compare the position of condyle between these two CBCT images. In the in vitro study, standard dental plaster casts with resin ball markers attached to the base were mounted onto a fully adjustable articulator in the intercuspal position. The dental casts were scanned by an extraoral scanner to establish digital models. The ultrasonic jaw motion tracking device was used to obtain simulated jaw movements on the articulator, which was repeated for three times. The digital models and data of jaw movements were merged in one coordination with the aid of bite forks. The jaw position of repositioning splint was determined by adjusting data of jaw movements, each of which was used to determine three vertical jaw positions 4 mm, 5 mm, and 6 mm with the horizontal jaw position of protrusion 2 mm. The virtual articulators with differently adjusted jaw movements were applied in designing repositioning splints, and the final repositioning splints and virtual jaw relationships were exported in STL format. Then the repositioning splints were fabricated with additive manufacturing technique and tried in plaster casts on the mechanical articulator, which were scanned and the jaw relationships on the mechanical articulator were exported later. The virtual jaw relationships and scanned jaw relationships were registered according to lower models and displacement of upper models was calculated. Ball markers were fit to acquire the coordinates of centers and absolute difference values of centers along three coordinating axes X, Y, and Z were calculated. One-way analysis of variance was conducted using SPSS 18.0 software to compare deviations of the three different vertical jaw relationships in two-side test and the significance level was 0.05. RESULTS: With the aid of multi-source data fusion and individualized jaw motion, the clinical workflow of determining jaw position of repositioning splint was preliminarily established. The designed jaw position was realized on the right and the condyle was more inferior than the designed position on the left. Both displacement of the upper models and absolute difference values of centers showed no significant differences (P>0.05) in different vertical jaw dimensions. The displacement of the upper models was (0.25±0.04) mm. The absolute difference values of centers along the three coordinating axes X, Y, and Z were respectively (0.08±0.01) mm, (0.30±0.02) mm, and (0.21±0.04) mm. CONCLUSION: A novel method of determining the jaw position of repositioning splint with the aid of digital technique is established. It is proved to be feasible by try-in after multi-data fusion, computer-aided design and computer-aided manufacturing. As is shown in vitro, it is accurate to apply this method in adjusting jaw position. Further clinical trial will be designed to evaluate its clinical effect.

[Accuracy of three intraoral scans for primary impressions of edentulous jaws].

OBJECTIVE: To provide a reference for using intraoral scanners for making clinical diagnostic dentures of edentulous jaws by comparing the accuracy of three intraoral scanners for primary impression and jaw relation record of edentulous jaws. METHODS: This study contained 6 primary impressions of the edentulous patients. Each of the impressions consisted of the maxillary primary impression, the mandibular primary impression and the jaw relation record. For each of them, a dental cast scanner (Dentscan Y500) was used to obtain stereolithography (STL) data as reference scan, and then three intraoral scanners including i500, Trios 3 and CEREC Primescan were used for three times to obtain STL data as experiment groups. In Geomagic Studio 2013 software, trueness was obtained by comparing experiment groups with the reference scan, and the precision was obtained from intragroup comparisons. Registered maxillary data of the intraoral scan with reference scan, the morphological error of jaw relation record was obtained by comparing jaw relation record of the intraoral scan with the reference scan. Registered mandibular data with jaw relation record of intraoral scan and the displacement of the jaw position were evaluated. Independent samples t test and Mann-Whitney U test in the SPSS 20.0 statistical software were used to statistically analyze the trueness, precision and morphological error of jaw relation record of three intraoral scanners. The Bland-Altman diagram was used to evaluate the consistency of the jaw relationship measured by the three intraoral scanners. RESULTS: The trueness of i500, Trios 3 and CEREC Primescan scanners was (182.34±101.21) µm, (145.21±71.73) µm, and (78.34±34.79) µm for maxilla; (106.42±21.63) µm, and 95.08 (63.08) µm, (78.45±42.77) µm for mandible. There was no significant difference in trueness of the three scanners when scanning the maxilla and mandible(P>0.05). The precision of the three scanners was 147.65 (156.30) µm, (147.54±83.33) µm, and 40.30 (32.80) µm for maxilla; (90.96±30.77) µm, (53.73±23.56) µm, and 37.60 (93.93) µm for mandible. The precision of CEREC Primescan scanner was significantly better than that of the other two scanners for maxilla (P<0.05). Trios 3 and CEREC Primescan scanners were significantly better than i500 scanner for mandible (P<0.05). The precision of the i500 and Trios 3 scanners for mandible was superior to maxilla (P<0.05). The upper limit of 95% confidence intervals of trueness and precision of three scanners for both maxilla and mandible were within ±300 µm which was clinically accepted. The morphological error of jaw relation record of the three scanners was (337.68±128.54) µm, (342.89±195.41) µm, and (168.62±88.35) µm. The 95% confidence intervals of i500 and Trios 3 scanners were over 300 µm. CEREC Primescan scanner was significantly superior to i500 scanner(P<0.05).The displacement of the jaw position of the three scanners was (0.83±0.56) mm, (0.80±0.45) mm, and (0.91±0.75) mm for vertical dimension; (0.79±0.58) mm, (0.62±0.18) mm, and (0.53±0.53) mm for anterior and posterior directions; (0.95±0.59) mm, (0.69±0.45) mm, and (0.60±0.22) mm for left and right directions. The displacement of the jaw position of the three scanners in vertical dimension, anterior and posterior directions and the left and right directions were within the 95% consistency limit. CONCLUSION: Three intraoral scanners showed good trueness and precision. The i500 and Trios 3 scanners had more errors in jaw relation record, but they were used as primary jaw relation record. It is suggested that three intraoral scanners can be used for obtaining digital data to make diagnostic dentures and individual trays, reducing possible deforming or crack when sending impressions from clinic to laboratory.

[Accuracy of intercuspal occlusion in 3D reconstruction with the dental articulator position method].

OBJECTIVE: To evaluate the three-dimensional (3D) reconstruction accuracy of the intercuspal occlusion (ICO) of the dental casts, by the dental articulator position method, and provide a reference for clinical application. METHODS: The standard dental casts in ICO were mounted on average values articulator, and five pairs of milling resin cylinders were respectively attached to the base of both the casts. 100 µm articulating paper and occlusal record silicone rubber were used to detect the occlusal contact number between the posterior teeth of casts mounted on articulator in ICO. The occlusal contact numbers NA detected by the two methods were calculated simultaneously, as the reference. After the upper and lower casts were scanned separately, and the buccal data of casts in ICO were scanned with the aid of the dental articulator position, registration was carried out utilizing the registration software. Then the digital casts mounted in ICO as well as the buccal occlusal data were saved in standard tessellation language (STL) format. Geomagic Studio 2013 software was used to analyze the contact number NS between digital upper and lower casts by the "deviation analysis" function. The differences were compared between NS and NA, to evaluate the sensitivity and positive predict value (PPV) of the model scanner to reproduce the occlusal contact with the aid of dental articulator position. The distance DR between the centers of the circles at the top surface of the upper and lower corresponding cylinders was obtained by the three-coordinate measuring system Faro Edge, as the reference value. The Geomagic Studio 2013 software was used to construct the cylinders of digital casts and the distance DM between the centers of the circles at the top surface of the corresponding cylinders were measured, as the test value. The one-sample T test was used to analyze the variable differences between DM and DR. RESULTS: The PPV of reproducing the occlusal contact point was 0.76 and sensitivity was 0.81. The distance error of the opposite cylinder was (0.232±0.089) mm. There was no statistical difference between the feature points 5-5', while there were statistical differences between the other feature points. CONCLUSION: By the dental articulator position method, the model scanner reproduces the occlusal contact point with high sensitivity and PPV, and that meets clinical needs. Meanwhile, the distance between the feature points is greater than the reference value, which will lead to occlusal disturbance, and require clinical grinding.

[Visual sensitivity threshold of lateral view of nasolabial Angle changes in edentulous jaw patients].

OBJECTIVE: To study the visual sensitivity threshold of physician's naked eye to the difference of nasolabial angle in edentulous jaw patients, and to provide a reference value for the study of aesthetic evaluation of soft tissue profile for the difference of nasolabial angle that can be recognized by human eyes. METHODS: Three-dimensional facial images of three edentulous patients with different diagnostic dentures introoral were obtained. Lateral screenshots of each patient's three-dimensional facial image with the same scale were obtained by using reverse engineering software (Geomagic studio 2014).The screenshot of the patient's three-dimensional facial image with suitable lip support (The suitable lip support was confirmed by both patients and prosthodontists who had clinical experience for more than 20 years) was taken as the reference picture, and the remaining pictures were grouped with it respectively. All the pictures were observed in random order by the subjects. Fifteen dentists were asked to judge the difference of nasolabial angle between the two pictures of each group on the computer screen. The difference of nasolabial angle between the two pictures in each group was measured and calculated. The ROC curve was drawn, and the best cut-off value was calculated as the visual sensitivity threshold. RESULTS: The data of the 15 subjects were used to draw ROC curves separately. The maximum and minimum best cut-off values were 5.55 degrees and 3.12 degrees respectively. The ROC curve of the whole 15 subjects was drawn after data aggregation, and the best cut-off value was 5.36 degrees (AUC=0.84>0.5, P=0.000<0.05). When the difference of nasolabial angle was above 5.36 degrees, the subjects could recognize it effectively. CONCLUSION: There is a visual limit in the observation of the nasolabial angle with the naked eye. In this study, a visual sensitivity threshold of 5.36 degrees for the difference of the nasolabial angle was obtained. The difference of nasolabial angle below this value can be regarded as no clinical significance. This result provides a reference value for human eyes to recognize the difference of nasolabial angle in soft tissue profile aesthetic evaluation. It can be applied to the aesthetic evaluation of soft tissue profile and can be used as the error level of related research with nasolabial angle as an index for accuracy evaluation.