Research progress and application prospect of stem cells in inflamed dental tissues on periodontal bone regeneration / 中华口腔医学杂志

Tissue engineering has become a research hotspot regarding periodontal bone regeneration in recent years. Generally, stem cells used in periodontal tissue engineering are derived from healthy dental tissues, while restricted due to the strict indication of tooth extraction and limited sources. Stem cells in inflamed dental tissues mainly derive from inflamed pulp, periapical and periodontal tissues. Stem cells in inflamed dental tissues are abundant and retain most of the basic characteristics of stem cell compared with the ones derived from healthy dental tissues, which can be a promising source of stem cells for periodontal bone regeneration. In this review, we summarize the current application and prospect of stem cells in inflamed dental tissues on periodontal bone regeneration, and then discuss their feasibility as seed cells, in order to provide a reference for future research and clinical application of stem cells in inflamed dental tissues.

Advances in the periodontal surgical flaps techniques to preserve gingival papilla / 中华口腔医学杂志

Papilla preservation in periodontal surgery is not only beneficial to maintain postoperative aesthetics and good oral hygiene but also contributes to obtaining good periodontal regeneration outcomes. Various periodontal flaps have been designed to preserve the gingival papilla, which constitutes the clinical basis for periodontal open flap debridement and periodontal regeneration surgery. A comprehensive understanding of their design purpose, indications, and technical key points will help clinicians to choose the optimal surgical plan, and thus improve the clinician's treatment levels, and obtain good clinical outcomes. Therefore, this article aims to introduce the design background, indications, and technical key points of various surgical flaps, such as papilla preservation technique, modified papilla preservation technique, simplified papilla preservation flap, etc.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Sitagliptin inhibits lipopolysaccharide-induced inflammatory response in human gingival fibroblasts by blocking nuclear factor-κB signaling pathway / 华西口腔医学杂志

OBJECTIVES@#This study was performed to clarify the effects of sitagliptin on @*METHODS@#Healthy gingival samples were collected from the donors. HGFs were isolated with enzymic digestion method and identified. The effects of LPS and sitagliptin on cell viability were detected by cell-counting kit-8 (CCK8). The mRNA levels of inflammatory cytokines, namely, interleukin (IL)-6, IL-8, C-C motif ligand 2 (CCL2), and superoxide dismutase 2 (SOD2), were evaluated by quantity real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA) was used to measure the secretion protein levels of IL-6, IL-8, and CCL2. Western blot analysis was used to further investigate the activation of nuclear factor (NF)-κB signaling pathway. The effect of NF-κB pathway inhibitor BAY11-7082 on LPS-induced HGF inflammatory cytokines at the gene level was verified by qRT-PCR.@*RESULTS@#Low concentrations of sitagliptin (0.1, 0.25, and 0.5 µmol·L@*CONCLUSIONS@#Sitagliptin could significantly inhibit LPS-induced HGF inflammatory response by blocking the NF-κB signaling pathway activation.

Clinical value of serum CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer.</p><p><b>METHODS</b>One hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis.</p><p><b>RESULTS</b>On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor (P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4 (P=0.006, P=0.002).</p><p><b>CONCLUSIONS</b>Tumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.</p>

Quantitative detection of human cytomegalovirus in aggressive and chronic periodontitis lesions / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To establish a quantitative real-time PCR assay for the detection of human cytomegalovirus (HCMV) DNA load in subgingival specimens from the patients with aggressive and chronic periodontitis, and to investigate the relationship between HCMV infection and the periodontal status.</p><p><b>METHODS</b>A total of 114 subgingival plaque specimens were taken from 18 subjects with aggressive priodontiti (AgP), 24 subjects with chronic periodontitis (CP) and 15 healthy control subjects. Standard quantification was performed with recombinant plasmid containing a conserved fragment of HCMV. The SYBR Green I fluorescent quantitative real-time PCR assay was established based on positive plasmid. HCMV DNA load in the specimens were detected with quantitative real-time PCR based on SYBR Green I fluorescence.</p><p><b>RESULTS</b>HCMV were detected in 58.3% of AgP sites and 41.7% of CP sites, however, only 6.7% of periodontally-healthy sites were HCMV positive. The detection rate of HCMV in periodontitis lesions was significantly higher than in periodontal health (P < 0.01). High copy-counts more than 10(4) of HCMV were detected in 33.3% of AgP sites, which were significantly higher than in CP sites (10.4%) (P < 0.05).</p><p><b>CONCLUSION</b>Subgingival infection with HCMV is closely associated with periodontitis. Active HCMV infection may be related to the rapid tissue destruction of AgP.</p>

Biological effects of phenytoin on cultured human periodontal ligament fibroblasts in vitro / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the biological effects of phenytoin (PHT) on cultured human periodontal ligament fibroblasts (hPDLF), and explore the possibility of its accelerating periodontal regeneration.</p><p><b>METHODS</b>Increasing concentrations of PHT (1, 5, 20, 100, 500, 2 500 mg/L) were added into the medium of the fourth passage of cultured hPDLF, respectively. After co-incubated for 3 days, cell proliferation activity, the total amount of protein and alkaline phosphatase (ALP) activity were detected. Mineralized sodium and PHT (20, 100, 500 mg/L) were added into the medium of the fourth passage hPDLF. After co-incubated, the mineralized nodules formation were detected by Von Kossa staining. The third passage hPDLF were stimulated by PHT (20, 100 mg/L), bone morphogenetic protein-2 (BMP-2) concentration was analyzed by enzyme linked immunosorbent sandwich assay (ELISA).</p><p><b>RESULTS</b>At the concentration of 20 or 100 mg/L, PHT significantly enhanced the proliferating activity and ALP activity of hPDLF (P<0.01). PHT at 100 mg/L could increase protein synthesis of hPDLF (P<0.05). The capability of mineralization and BMP-2 expression of hPDLF were increased significantly (P<0.01) in 100 mg/L group when compared with that in the control group. However, higher concentration (2 500 mg/L) not only changed cell morphology, but also significantly inhibited cell activity.</p><p><b>CONCLUSION</b>The results suggested that proper doses of PHT could promote proliferation and biosynthesis and also enhance osteogenesis by increasing the differentiation, mineralization and BMP-2 expression of hPDLF while higher concentrations of PHT had cytotoxic effect.</p>

Clinical effect of minocycline as adjunctive therapy to scaling and root planning on treatment of chronic periodontitis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of minocycline as an adjunct to scaling and root planning (SRP) in treating chronic periodontitis.</p><p><b>METHODS</b>64 male smokers with moderate to advanced periodontitis were randomly divided into two groups: SRP alone (SRP) and SRP plus minocycline (SRP+M). All clinical parameters including plaque index (Pll), gingival index (GI), bleeding on probing (BOP), probing depth (PD) and attachment gain were recorded at baseline, 3 and 6 months after treatment.</p><p><b>RESULTS</b>According to PlI, GI and BOP, there was no significant difference between the two groups at 3 and 6 months after periodontal therapy (1 > 0.05). However, PD reduction and attachment gain were significantly greater for SRP+M than that for SRP (P < 0.05). For SRP+M and SRP groups, PD reduction were 1.98 mm and 1.32 mm, and attachment gain were 1.87 mm and 1.14 mm respectively. Deep pockets in SRP+M group showed more obvious PD reduction (3.48 mm versus 2.21 mm, P < 0.01) and attachment gain (2.62 mm versus 1.23 zmm, P < 0.01) than that in SRP group.</p><p><b>CONCLUSION</b>Treatment with SRP plus locally delivered minocycline is more effective than SRP alone in male smokers with chronic periodontitis. Mechanical debridement plus locally delivered antibiotics are recommended especially for smokers with deep pocket periodontitis.</p>

Expression of epidermal growth factor receptor in human periodontal ligament cells during their mineralization in vitro / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of epidermal growth factor receptor (EGFR) during the mineralization of human periodontal ligament cells (hPDLC) in vitro.</p><p><b>METHODS</b>Studies using specific antibodies to immunolocalize EGFR in the mineral differentiating hPDLC were undertaken to investigate the different expression during the inducing process. In situ hybridization and RT-PCR technique were used to investigate the transcripts encoding the protein of EGFR.</p><p><b>RESULTS</b>The results showed that immunocytochemical labeling gradually decreased following the elong of the induce time, downing to nearly negative at the 4th week and the signal of EGFR transcripts was weaker in the induced hPDLC than that in uninduced.</p><p><b>CONCLUSION</b>EGFR has a negative regulation function during the mineralization of hPDLC.</p>

Culture and phenotype characteristics of mouse dental follicle cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To establish a method for isolating and culturing mouse dental follicle cells and to study the phenotype characteristics of dental follicle cells.</p><p><b>METHODS</b>Mandibular first molars from 9 day old Balb/c mice were digested with 1% trypsin, subsequently, and the dental follicle was enucleated from the tooth germ and cultured. The shape and ultrastructural appearance of dental follicle cells were observed under phase-contrast microscope and scanning electron microscope (SEM). Immunocytochemistry was used to detect the expression of alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteopontin (OPN).</p><p><b>RESULTS</b>Three types of cells were isolated: some were cuboidal/polygonal; some were elongated, spindle-shaped, fibroblast-like cells; and a minor, third cell type was very thin and elongated. The cytoplasm of the first two cell types was filled with abundant granules. The cells were pleomorphism under SEM and had many filipodia and microvilli. According to whether there were filaments overlying the surface, the cells could be divided into two subtypes. Some but not all follicle cells expressed ALP, BSP and OPN.</p><p><b>CONCLUSION</b>The cultured dental follicle cells consisted of several cell phenotypes and had the potential of differentiating into cementoblasts, periodontal ligament fibroblasts and osteoblasts.</p>

The effect of bFGF on proliferation of periodontal fibroblast-like cells of dogs / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of basic fibroblast growth factor(bFGF) on proliferation of periodontal fibroblast-like cells in vivo.</p><p><b>METHODS</b>A U-shaped osseous defect was produced on the buccal side of the mesial root. Four posterior teeth were conducted in four quadrants. Each quadrant included 4 groups: control, bFGF, expanded polytetrafluoroethylene(ePTFE) membrane, bFGF + ePTFE. Each time the 4 teeth sites in one quadrant were operated weekly and each dog experienced 4 times of operations. Bromodeoxyuridine(BrdU) was injected 1 hour prior to sacrificing the dogs at 4 weeks after first surgery. Immunohistochemical method was applied to count the BrdU-labeled fibroblast-like cells.</p><p><b>RESULTS</b>The number of BrdU-labeled cells reached the maximum at the 2nd week among all groups and then, decreased with time. Both bFGF and bFGF + ePTFE treated group had significantly more BrdU+ cells than remained control or ePTFE groups (P < 0.05) at 1st, 2nd weeks after surgery.</p><p><b>CONCLUSION</b>2 weeks after periodontal surgery is active phase of proliferation of periodontal fibroblasts. bFGF enhances fibroblast proliferation in early periodontal wound healing, and in turn accelerate periodontal regeneration.</p>

Effects of minocycline on biobehavior of human periodontal ligament cells in vitro / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the influence of minocycline on the proliferation and biosynthesis of human periodontal ligament cells (HPDLCs) in vitro.</p><p><b>METHODS</b>Various concentrations of minocycline (1, 5, 20, 100, 500, 2 500 mg/L) were added to the medium of cultured HPDLCs respectively. After co-incubated for 2 days, cell morphology was observed under reverse microscope, cell proliferation activity was assayed using MTT, the total amount of protein was detected with Coumassie Bright Blue method and DNA synthesis was measured by (3)H-TdR.</p><p><b>RESULTS</b>The presence of minocycline not exceeding 500 mg/L in the medium resulted in no morphological change of HPDLCs. Moreover, at a concentration range of 5 to 100 mg/L, minocycline significantly enhanced the proliferative activity and biosynthesis of HPDLCs (P < 0.01). However, higher concentration (2 500 mg/L) not only changed cell morphology under microscope, but also significantly inhibited cellular activity.</p><p><b>CONCLUSIONS</b>The results suggest that proper doses of minocycline could promote biobehavior of HPDLCs, while higher concentrations of minocycline had cytotoxic effect which may intervene affect tissue repair and regeneration.</p>

Biological effects of tetracycline on cultured human periodontal fibroblasts / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To explore the biological effects of tetracycline on cultured human periodontal ligament fibroblasts (HPDLFs).</p><p><b>METHODS</b>Increasing concentrations of tetracycline (1, 5, 20, 100, 500, 2500 microg/ml) were added to the medium of cultured HPDLFs, respectively. After co-incubated for 2 days, cell morphology was observed under reverse microscope, meanwhile, cell proliferation activity was assayed using MTT, the total amount of protein was detected with Coumassie Bright Blue method and DNA synthesis was measured by 3H-TdR.</p><p><b>RESULTS</b>Over a concentration range of 1 to 100 microg/ml, cells demonstrated a normal appearance, spindle or fusiform shaped. Moreover, at a concentration range of 20 to 100 microg/ml, tetracycline significantly enhanced the proliferating activity and biosynthesis of HPDLFs (P < 0.01). However, higher concentration (2500 microg/ml) not only changed cell morphology, but also significantly inhibited cellular activity.</p><p><b>CONCLUSION</b>The results suggested that proper doses of tetracycline could promote proliferation and biosynthesis of HPDLFs while higher concentrations of tetracycline had cytotoxic effect.</p>

The effect of periodontal initial therapy on circulating TNF-alpha and HbA1C in type 2 diabetes patients with periodontitis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of periodontal initial therapy on type 2 diabetes patients with periodontitis.</p><p><b>METHODS</b>15 type 2 diabetes patients with periodontitis were selected. Their body mass index (BMI), sulcus bleeding index (SBI), probing depth (PD), circulating tumor necrosis factor-alpha (TNF-alpha) concentration, and the value of glycosylated hemoglobin (HbA1C), triglycerides (TG) and cholesterol (CHOL) were assessed respectively before and 4-6 weeks after periodontal initial therapy.</p><p><b>RESULTS</b>After initial therapy, SBI, PD, circulating TNF-alpha concentration, and the value of HbA1C and TG were reduced significantly (P<0.05), while there were no significant differences in BMI and CHOL value (P>0.05).</p><p><b>CONCLUSIONS</b>Periodontal initial therapy can effectively reduce HbA1C value in type 2 diabetes patients with periodontitis, possibly through the reduction of circulating TNF-alpha concentration.</p>