[Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients].

Objective: The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored. Methods: (1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed. Results: (1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95%CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95%CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions: Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

[Technical essentials and safety analysis of "rolling carpet" cytoreduction surgery in stage â ¢c epithelial ovarian cancer].

Objective: To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy （"rolling carpet" surgery） in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality. Methods: From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent "rolled carpet" CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of "rolled carpet" CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of "rolling carpet" CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups. Results: (1) Clinicopathological features: the age of patients in "rolling carpet" CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the "rolled carpet" CRS group, all patients （100%, 30/30） were performed optimal CRS, reaching completeness of cytoreduction score （CC score）, named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients （77%, 23/30） reached CC-0 score, 5 cases （17%, 6/30） reached CC-1 score, 2 cases （7%, 2/30） reached CC-2 score, and there were statistical significance between the two groups (P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the "rolled carpet" CRS group and the traditional CRS groups (P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion: It is safe and feasible to perform "rolled carpet" CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.

Addition of bevacizumab to neoadjuvant chemotherapy for Stage IV ovarian serous adenocarcinoma with multiple lymph node metastases: a case report.

A 50-year-old female patient was diagnosed with Stage IV ovarian serous adenocarcinoma with multiple lymph node metastases. The CA-125 level normalized after four cycles of neoadjuvant chemotherapy (NACT) using paclitaxel, nedaplatin, and bevacizumab (BEV) before surgery. A positron emission tomography-computed tomography (PET-CT) scan showed significantly reduced bilateral adnexal masses after NACT fluorodeoxyglucose (FDG) metabolism in multiple lymph nodes was inhibited significantly, and the number and sites of metastatic lesions were decreased. The patient underwent optimal cytoreductive surgery. Chemotherapy was continued after surgery and image-guided radiation therapy (IGRT) (40 Gy) was applied for the remaining lymph nodes in the pelvic cavity and cervicothoracic region. No sign of recurrence has been observed in this patient nine months after surgery. The patient achieved a satisfactory outcome and no serious side effects were observed. Therefore, addition of BEV to NACT is a new method for the pre-operative treatment of advanced ovarian cancer.

BEP for high-risk gestational trophoblastic tumor: results from a cohort of 45 patients.

AIM: To evaluate the effectiveness and safety of combination chemotherapy of bleomycin, etoposide, and cisplatin (BEP) regimen in patients with high-risk gestational trophoblastic neoplasia (GTN). MATERIALS AND METHODS: The authors analyzed the clinical response, toxicity, and the occurrence of secondary tumors of 45 patients with high-risk GTN under BEP. RESULTS: The total complete remission (CR) rate of BEP regimen was 88.89% (40/45). Five patients developed drug-resistance after average 4.8 courses of BEP, and the regimen converted to etoposide, methotrexate, and dactinomycin (EMA)/cyclophosphamide and vincristine sulfate (CO). Ultimately, four cases achieved CR and one case died of cancer. There were no severe anaphylaxis and obvious impairment of cardiac, liver, pulmonary and kidney function, except one patient who developed grade IV bone marrow suppression and worsened pulmonary fibrosis after chemotherapy. None of survival patients developed secondary tumor during the follow-up. CONCLUSION: For young high-risk GTN patients, BEP may represent a safe and effective regimen.

First Report of Pepper Fruit Rot Caused by Fusarium concentricum in China.

Pepper (Capsicum annuum L.) is an important vegetable crop worldwide. Some Fusarium species can cause pepper fruit rot, leading to significant yield losses of pepper production and, for some Fusarium species, potential risk of mycotoxin contamination. A total of 106 diseased pepper fruit samples were collected from various pepper cultivars from seven provinces (Gansu, Hainan, Heilongjiang, Hunan, Shandong, Shanghai, and Zhejiang) in China during the 2012 growing season, where pepper production occurs on approximately 25,000 ha. Pepper fruit rot symptom incidence ranged from 5 to 20% in individual fields. Symptomatic fruit tissue was surface-sterilized in 0.1% HgCl2 for 1 min, dipped in 70% ethanol for 30 s, then rinsed in sterilized distilled water three times, dried, and plated in 90 mm diameter petri dishes containing potato dextrose agar (PDA). After incubation for 5 days at 28°C in the dark, putative Fusarium colonies were purified by single-sporing. Forty-three Fusarium strains were isolated and identified to species as described previously (1,2). Morphological characteristics of one strain were identical to those of F. concentricum. Aerial mycelium was reddish-white with an average growth rate of 4.2 to 4.3 mm/day at 25°C in the dark on PDA. Pigments in the agar were formed in alternating red and orange concentric rings. Microconidia were 0- to 1-septate, mostly 0-septate, and oval, obovoid to allantoid. Macroconidia were relatively slender with no significant curvature, 3- to 5-septate, with a beaked apical cell and a foot-shaped basal cell. To confirm the species identity, the partial TEF gene sequence (646 bp) was amplified and sequenced (GenBank Accession No. KC816735). A BLASTn search with TEF gene sequences in NCBI and the Fusarium ID databases revealed 99.7 and 100% sequence identity, respectively, to known TEF sequences of F. concentricum. Thus, both morphological and molecular criteria supported identification of the strain as F. concentricum. This strain was deposited as Accession MUCL 54697 (http://bccm.belspo.be/about/mucl.php). Pathogenicity of the strain was confirmed by inoculating 10 wounded, mature pepper fruits that had been harvested 70 days after planting the cultivar Zhongjiao-5 with a conidial suspension (1 × 106 spores/ml), as described previously (3). A control treatment consisted of inoculating 10 pepper fruits of the same cultivar with sterilized distilled water. The fruit were incubated at 25°C in a moist chamber, and the experiment was repeated independently in triplicate. Initially, green to dark brown lesions were observed on the outer surface of inoculated fruit. Typical soft-rot symptoms and lesions were observed on the inner wall when the fruit were cut open 10 days post-inoculation. Some infected seeds in the fruits were grayish-black and covered by mycelium, similar to the original fruit symptoms observed at the sampling sites. The control fruit remained healthy after 10 days of incubation. The same fungus was isolated from the inoculated infected fruit using the method described above, but no fungal growth was observed from the control fruit. To our knowledge, this is the first report of F. concentricum causing a pepper fruit rot. References: (1) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006. (2) K. O'Donnell et al. Proc. Nat. Acad. Sci. USA 95:2044, 1998. (3) Y. Yang et al. 2011. Int. J. Food Microbiol. 151:150, 2011.

Rapid analysis of pyrethroid insecticides in aquaculture seawater samples via membrane-assisted solvent extraction coupled with gas chromatography-electron capture detection.

A simple, efficient, and environmentally friendly membrane-assisted solvent extraction (MASE) method for the extraction and preconcentration of six pyrethroid insecticides from aquaculture seawater samples followed by gas chromatography-electron capture detection (GC-ECD) was successfully proposed. The operating conditions for MASE, such as the extraction solvent, solvent volume, NaCl concentration, stirring rate, extraction time, and temperature, were optimized. Compared to conventional Florisil-solid phase extraction (SPE), higher extraction recoveries (85.9% to 105.9%) of three spiked levels of the six pyrethroid pesticides in aquaculture seawater were obtained using MASE, and the RSD values were lower than 7.9%. The limits of detection (LOD, signal-to-noise ratio (S/N)=3) and quantification (LOQ, S/N = 10) were in the range of 0.037-0.166 and 0.12-0.55 µg L(-1), respectively. The results demonstrate the excellent applicability of the MASE method in analyzing the six pyrethroid pesticides in aqueous samples. The proposed method exhibited a high potential for routine monitoring analysis of pyrethroid insecticides in seawater samples.

Synthesis and mechanical properties of interconnected carbon nanofiber network reinforced polydimethylsiloxane composites.

Carbon nanofiber (CNF) reinforced elastomer composites with light weight, sustainability of large deformation, chemical stability, corrosion and fatigue resistance, and vibration and noise reduction capability can have positive impact on a wide range of applications. However, this type of composite is still a under studied research area due to the difficulties in material handling and processing. To improve processing control and reproducibility for large scale engineering applications, cost effective carbon nanofibers (CNFs) in form of interconnected porous network structure were used as nanofillers. Processing, microstructure and mechanical properties of carbon nanofibers reinforced polydimethylsiloxane (PDMS) have been studied. Mechanical measurements on the composites show that the CNF-PDMS interfacial bonding can be until failure, interfacial debonding happens in the CNF-PDMS composites and the resulted permanent deformation stabilizes with increasing load-unload cycles with significant energy dissipation.

Protective effect of the new prepared Atractylodes macrocephala Koidz polysaccharide on fatty liver hemorrhagic syndrome in laying hens.

Fatty liver hemorrhage syndrome (FLHS) is the most common noninfectious cause of death in backyard chickens worldwide, which can cause a sudden drop in egg production in the affected flocks and cause huge losses to the laying hens breeding industry. In this study, we prepared polysaccharide from Atractylodes macrocephala Koidz (PAMK) by one-step alcohol precipitation. The structural analysis found that PAMK with a molecular weight of 2.816 × 103 Da was composed of glucose and mannose, in a molar ratio of 0.582 to 0.418. Furthermore, we investigated the hepatoprotective effects of PAMK on high-energy and low-protein (HELP) diet-induced FLHS in laying hens. The results showed that the hens' livers of the HELP diet showed yellowish-brown, greasy, and soft, whereas the supplement of PAMK (200 mg/kg or 400 mg/kg) could alleviate such pathological changes. The liver index, the abdominal fat percentage, and liver injury induced by the HELP diet were reduced in PAMK (200 mg/kg or 400 mg/kg). Supplementing 200 mg/kg or 400 mg/kg PAMK showed improvements of the antioxidant capacity in laying hens. Furthermore, we found that the HELP diet increased the expression of hepatic lipogenesis genes and decreased the expression of fatty acid ß-oxidation genes, which could be reversed by 200 mg/kg or 400 mg/kg PAMK supplementation. Nevertheless, there is no difference between the addition of 40 mg/kg PAMK and the HELP group. Collectively, these results showed that PAMK supplements could ameliorate HELP diet-induced liver injury through regulating activities of antioxidant enzymes and hepatic lipid metabolism. Therefore, PAMK could be a potential feedstuff additive to alleviate FLHS in laying hens.

Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity.

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, "Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity, by P.-F. Su, S.-Q. Song, published in Eur Rev Med Pharmacol Sci 2018; 22 (20): 6864-6872-DOI: 10.26355/eurrev_201810_16155-PMID: 30402851" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16155.

Quantitative description of the effect of stratification on dormancy release of grape seeds in response to various temperatures and water contents.

The effect of stratification on dormancy release of grape seeds crossing from the sub- to the supraoptimal range of temperatures and water contents was analysed by modified threshold models. The stratification impacted on dormancy release in three different ways: (i) dormancy was consistently released with prolonged stratification time when stratified at temperatures of <15 degrees C; (ii) at 15 degrees C and 20 degrees C, the stratification effect initially increased, and then decreased with extended time; and (iii) stratification at 25 degrees C only reduced germinable seeds. These behaviours indicated that stratification could not only release primary dormancy but also induce secondary dormancy in grape seed. The rate of dormancy release changed linearly in two phases, while induction increased exponentially with increasing temperature. The thermal time approaches effectively quantified dormancy release only at suboptimal temperature, but a quantitative method to integrate the occurrence of dormancy release and induction at the same time could describe it well at either sub- or supraoptimal temperatures. The regression with the percentage of germinable seeds versus stratification temperature or water content within both the sub- and supraoptimal range revealed how the optimal temperature (T(so)) and water content (W(so)) for stratification changed. The T(so) moved from 10.6 degrees C to 5.3 degrees C with prolonged time, while W(so) declined from >0.40 g H2O g DW(-1) at 5 degrees C to approximately 0.23 g H2O g DW(-1) at 30 degrees C. Dormancy release in grape seeds can occur across a very wide range of conditions, which has important implications for their ability to adapt to a changeable environment in the wild.

Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity.

OBJECTIVE: The aberrant increasing expression of mammalian target of rapamycin (mTOR) participates in tumor occurrence and drug resistance. It has been found elevation of mTOR expression but reducing miR-107 expression in glioma tissues. Thus, we investigated the regulatory role of miR-107 on mTOR expression as well as glioma cell proliferation, apoptosis and cisplatin (DDP) resistance. PATIENTS AND METHODS: Dual luciferase reporter gene assay was applied to confirm targeted regulation between miR-107 and mTOR. Tumor tissues were collected from glioma patients, in parallel with normal tissues after brain contusion surgery. Expressions of miR-107, mTOR and p-mTOR were compared. DDP-resistant cell line U251/DPP was generated. U251/DPP cells were further treated with miR-107 mimic or si-mTOR to examine the change of miR-107, mTOR, p-mTOR and survivin levels. Flow cytometry was used to quantify the effect of DDP treatment on cell proliferation or apoptosis. RESULTS: Bioinformatics analysis revealed complementary binding sites between miR-107 and 3'-UTR of mTOR mRNA. Dual luciferase assay confirmed targeted regulation between miR-107 and mTOR. Compared to control group, in glioma tissues, mTOR and p-mTOR expressions were significantly elevated, while the level of miR-107 expression was markedly decreased. Of note, U251/DDP cells presented weakened apoptosis compared to U251 cells, with high levels of mTOR, p-mTOR and survivin and reduction of miR-107 expression. However, the transfection of miR-107 mimic and/or si-mTOR remarkably suppressed expressions of mTOR, p-mTOR and survivin in U251/DPP cells, weakened cell proliferation and enhanced apoptosis. CONCLUSIONS: We demonstrated that the level of miR-107 was correlated with DDP resistance in glioma cells. Over-expression of miR-107 decreased DPP resistance of glioma cells via inhibition of mTOR, which provides academic basis for the future anti-glioma therapy.

Effects of Dietary Selenium Against Lead Toxicity on mRNA Levels of 25 Selenoprotein Genes in the Cartilage Tissue of Broiler Chicken.

The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, little is known about the effect of Se on Pb toxicity and the expression pattern of selenoproteins in the cartilage of chicken. To investigate the effects of Se on Pb toxicity and the messenger RNA (mRNA) expressions of selenoproteins in cartilage tissue, an in vitro study was performed on 1-day-old broiler chickens (randomly allocated into four groups) with diet of different concentration of Se and Pb. After 90 days, the meniscus cartilage and sword cartilage tissue were examined for the mRNA levels of 25 selenoprotein genes. The results showed that Se and Pb influenced the expression of selenoprotein genes in the chicken cartilage tissue. In detail, Se could alleviate the downtrend of the expression of Gpx1, Gpx2, Gpx4, Txnrd2, Txnrd3, Dio1, Dio2, Seli, Selu, Sepx1, Selk, Selw, Selo, Selm, Sep15, Sepnn1, Sels, and Selt induced by Pb exposure in the meniscus cartilage. In the sword cartilage, Se alleviated the downtrend of the expression of Gpx2, Gpx3, Gpx4, Txnrd1, Txnrd2, Dio2, Dio3, Seli, Selh, SPS2, Sepx1, Selk, Selw, Selo, Selm, Sep15, Selpb, Sepn1, and Selt induced by Pb exposure. The present study provided some compensated data about the roles of Se against Pb toxicity in the regulation of selenoprotein expression.

[Evaluation of the effects of the ostiomeatal complex corrective surgery].

OBJECTIVE: To study the effects of the ostiomeatal complex corrective surgery (OCRS) for finding out more suitable surgical style for the nasal obstructive diseases. METHOD: 135 cases treated with OCRS were summed up and analyzed. RESULT: The effect is marked by comparison with the traditional surgery such as middle turbinectomy, ethmoidectomy etc. CONCLUSION: The developing direction of the nasal surgical treatment ought to recover the nasal physiological structure. The OCRS makes great efforts in this direction and the achievements have been confirmed.

Effects of tetrandrine, Fura 2-AM, and Bay k 8644 on platelet-activating factor release from rat peritoneal macrophages stimulated by lipopolysaccharides.

AIM: To study the relationship between the calcium and the release of platelet-activating factor (PAF) from rat peritoneal macrophages (PMø) stimulated by lipopolysaccharides (LPS). METHODS: The effects of tetrandrine (Tet), Fura 2-AM, and Bay k 8644 on the PAF release from rat PMø was investigated by the bio-assay of PAF. RESULTS: LPS stimulated PMø to release PAF, without increasing intracellular Ca2+ of PMø, Tet at 0.1, 1.0, 10, 100 mumol.L-1 and Fura 2-AM at 0.01, 0.1, 1.0, 10 mumol.L-1 could dose-dependently decrease the release of PAF (9.8 +/- 1.2, 6.5 +/- 1.6, 4.7 +/- 0.8, 3.4 +/- 0.4 microgram.L-1 and 9.2 +/- 1.7, 5.2 +/- 1.3, 3.7 +/- 0.4, 3.2 +/- 0.3 microgram.L-1, respectively, no drugs 11.8 +/- 1.2 micrograms.L-1), Bay k 8644 at 1.0, 5.0, 10 mumol.L-1 could dose-dependently increase the release of PAF (13.2 +/- 1.7, 16.2 +/- 1.4, 17.6 +/- 1.5 micrograms.L-1), and the effects of Tet and Fura 2-AM were completely or partly reversed by Bay k 8644 at 5.0 mumol.L-1. CONCLUSION: Although LPS did not increase intracellular Ca2+ of PMø, intracellular Ca2+ was necessary for PAF release from rat PMø stimulated by LPS.

Wear patterns of composite restorative resins in vivo; observations by scanning electron microscopy.

In this study, the wear pattern of seven commercial composite resins, one experimental composite and one dental amalgam were investigated. These materials were separately inserted in a separation preparation cavity of the patient's mouth. After clinical service for 3, 9 and 12 months the specimens were taken out and observed by scanning electron microscopy (SEM). It was found that the softer resin matrix wore away first while the inorganic filler particles showed no signs of abrasive wear, whereafter filler particles were loosened once there was no support of the resin matrix around them.

A study of surfaces developed on composite resins in vivo during 4.5 years; observations by SEM.

In this study seven commercial composite resins, one experimental composite and one dental amalgam were investigated. These materials were inserted into the cavities of denture molar teeth in different patients. After clinical service for 3, 9, 12, 24 and 54 months the specimens were removed and observed by scanning electron microscopy. The wear patterns of the filling materials and their changes with continuing clinical service for 4.5 years suggest that the abrasive mechanism of conventional composite resin is as follows. The softer resin matrix is worn away and inorganic filler particles are exposed, thereafter they loosen and fall off. As this process proceeds the composite resin is worn away. This process continues with time. In the case of microfilled composite, the organic fillers and resin matrix are worn away at the same rate. After long-term clinical service some cracks could be seen on the wear surface between the organic filler agglomerates and the resin matrix.