Objective:To investigate the protective effect of grape seed proanthocyanidin extract(GSPE) on fluoride-induced nephrotoxicity and study the possible role of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway.Methods:Twenty-four male Sprague-Dawley (SD) rats (aged 8 weeks, weighing 240 - 260 g) were randomly divided into four groups using a random number table: control group, GSPE group, sodium fluoride (NaF) group, and NaF + GSPE group, with 6 rats in each group. The control group was fed a standard diet for 28 d. The GSPE group was administered GSPE (100 mg/kg) via gavage daily for 28 d. The NaF group was fed a standard diet for 7 d, followed by NaF solution (600 mg/kg) for 21 d. A drinking-water-borne fluorosis rat model was established. The NaF + GSPE group was pretreated with GSPE (100 mg/kg) for 7 d follwed by NaF solution (600 mg/kg) for 21 d. At the end of the experiment, the levels of renal oxidative stress were assessed by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Renal function was evaluated by analyzing the levels of serum creatinine (Cr), blood urea nitrogen (BUN), and Urea. Renal pathological changes and apoptosis levels were examined using hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Additionally, the expression levels of Nrf2 signaling pathway-related proteins [Nrf2, heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO-1), and caspase-3] were detected by Western blot.Results:Compared with the control group, the NaF group had higher level of renal MDA, lower level of GSH, and lower activities of CAT and SOD( P < 0.001). Compared with the NaF group, the NaF + GSPE group had lower level of renal MDA, higher level of GSH, and higher activities of CAT and SOD ( P < 0.001). The serum Cr, BUN, and Urea levels were significantly elevated in the NaF group compared to the control group ( P < 0.001), while these parameters were significantly reduced in the NaF + GSPE group relative to the NaF group ( P < 0.001). The HE staining results showed that the glomerular volume increased and the basement membrane thickened; renal tubules disruption of cellular structure, with degeneration, dilation, or shedding of renal tubular epithelial cells; inflammatory cell infiltration can be seen in the renal interstitium in the NaF group of rats. Compared with the NaF group, the pathological changes in the NaF + GSPE group were significantly improved. The TUNEL results showed that the apoptosis rates of renal cells in the NaF and NaF + GSPE groups [(26.82 ± 2.25)%, (12.83 ± 1.32)%] were higher than those in the control group [(6.22 ± 0.62)%, P < 0.001], and in the NaF + GSPE group was lower than that in the NaF group ( P < 0.001). Compared with the control group, the NaF group showed expression levels of Nrf2 (nuclear), HO-1, NQO-1, activated caspase-3 protein were higher, while the expression level of Nrf2 (cytoplasmic) protein was lower. Compared with the NaF group, the NaF + GSPE group had higher expression levels of Nrf2 (nuclear, cytoplasmic), HO-1, and NQO-1 proteins, and lower expression level of activated caspase-3 protein ( P < 0.001). Conclusion:GSPE can alleviate the nephrotoxicity induced by fluoride, which may be related to activating the Nrf2 signaling pathway to enhance the body's antioxidant capacity and reduce the level of renal cell apoptosis.

Objective:To investigate the protective effect of grape seed proanthocyanidin extract(GSPE) on fluoride-induced nephrotoxicity and study the possible role of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway.Methods:Twenty-four male Sprague-Dawley (SD) rats (aged 8 weeks, weighing 240 - 260 g) were randomly divided into four groups using a random number table: control group, GSPE group, sodium fluoride (NaF) group, and NaF + GSPE group, with 6 rats in each group. The control group was fed a standard diet for 28 d. The GSPE group was administered GSPE (100 mg/kg) via gavage daily for 28 d. The NaF group was fed a standard diet for 7 d, followed by NaF solution (600 mg/kg) for 21 d. A drinking-water-borne fluorosis rat model was established. The NaF + GSPE group was pretreated with GSPE (100 mg/kg) for 7 d follwed by NaF solution (600 mg/kg) for 21 d. At the end of the experiment, the levels of renal oxidative stress were assessed by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Renal function was evaluated by analyzing the levels of serum creatinine (Cr), blood urea nitrogen (BUN), and Urea. Renal pathological changes and apoptosis levels were examined using hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Additionally, the expression levels of Nrf2 signaling pathway-related proteins [Nrf2, heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO-1), and caspase-3] were detected by Western blot.Results:Compared with the control group, the NaF group had higher level of renal MDA, lower level of GSH, and lower activities of CAT and SOD( P < 0.001). Compared with the NaF group, the NaF + GSPE group had lower level of renal MDA, higher level of GSH, and higher activities of CAT and SOD ( P < 0.001). The serum Cr, BUN, and Urea levels were significantly elevated in the NaF group compared to the control group ( P < 0.001), while these parameters were significantly reduced in the NaF + GSPE group relative to the NaF group ( P < 0.001). The HE staining results showed that the glomerular volume increased and the basement membrane thickened; renal tubules disruption of cellular structure, with degeneration, dilation, or shedding of renal tubular epithelial cells; inflammatory cell infiltration can be seen in the renal interstitium in the NaF group of rats. Compared with the NaF group, the pathological changes in the NaF + GSPE group were significantly improved. The TUNEL results showed that the apoptosis rates of renal cells in the NaF and NaF + GSPE groups [(26.82 ± 2.25)%, (12.83 ± 1.32)%] were higher than those in the control group [(6.22 ± 0.62)%, P < 0.001], and in the NaF + GSPE group was lower than that in the NaF group ( P < 0.001). Compared with the control group, the NaF group showed expression levels of Nrf2 (nuclear), HO-1, NQO-1, activated caspase-3 protein were higher, while the expression level of Nrf2 (cytoplasmic) protein was lower. Compared with the NaF group, the NaF + GSPE group had higher expression levels of Nrf2 (nuclear, cytoplasmic), HO-1, and NQO-1 proteins, and lower expression level of activated caspase-3 protein ( P < 0.001). Conclusion:GSPE can alleviate the nephrotoxicity induced by fluoride, which may be related to activating the Nrf2 signaling pathway to enhance the body's antioxidant capacity and reduce the level of renal cell apoptosis.

Objective: To retrospectively analyze distribution characteristics of pathogenic bacteria and their antimicrobial susceptibility in patients with diabetic foot osteomyelitis(DFO). Methods: Sixty cases of suspected DFO were collected from the Endocrinology Department of Henan Provincial People′s Hospital. After admission, bone biopsy was carried out to confirm the pathological diagnosis, and the pathogenic bacteria and drug sensitivity were determined by bone culture. In addition, bacterial culture was carried out in the basal tissue of the wound, and the results of bacterial culture were compared with those of bone culture. Results: Sixty patients were diagnosed as DFO after bone biopsy. Among the 60 patients, 45 patients underwent bone culture and basal tissue culture. There are 24 patients of whom the results were consistent, accounting for 53.3%. The positive rate of bone culture was 55.0%, there were 16 strains of gram-positive bacteria and 22 strains of gram-negative bacteria. Staphylococcus aureus(9 strains) occurrence was the most, common finding, followed by Escherichia coli(6 strains). The course of diabetic foot, albumin(ALB), and antibiotic usage rate before admission were lower in bone culture positive group than those in bone culture negative group, while white blood cell(WBC) and C-reactive protein(CRP) were higher in bone culture negative group(P<0.05). There was no significant difference in gender, age, course of diabetes, HbA_1C, and creatinine(CREA) levels between the two groups(P>0.05). The results of bone culture showed that Staphylococcus aureus was the main Gram-positive bacteria, which was more sensitive to vancomycin, tigecyclin, linezolid, etc. Escherichia coli was the main Gram-negative bacteria, which was more sensitive to tigecyclin, carbapenems, amikacin, etc. Conclusion Bone biopsy and bone culture should be carried out in cases for suspected DFO patients to identify the pathogenic bacteria, and the bone tissue should be preserved and obtained according to the operation specification before the application of antibiotics, and the appropriate antibiotics should be selected according to the drug sensitivity results.

Objective: To study the regulatory effects and possible mechanism of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) on chemotherapy sensitivity to cisplatin (DDP) of colorectal cancer (CRC)．Methods: A total of 112 pairs of matched cancer and adjacent non-cancerous tissues were obtained from the CRC patients who underwent surgical resection in the First Affiliated Hospital of Xinxiang Medical University betweenApril 2006 and March 2011.All specimens were confirmed by pathological examinations. Tumor tissues and corresponding adjacent non-cancerous tissues from 30 cisplatin-sensitive CRC patients and 30 cisplatin-resistant patients were selected. Human CRC cell lines (HT29, SW480, HCT116, RKO and LoVo) and normal colonic epithelial cell line NCM460 were also collected for this study; and DDP-resistant RKO/DDP and LoVo/DDP cell lines were constructed. siPVT1, siNC, LV-PVT1 and LV-NC were transfected into LoVo and RKO cells or LoVo/DDP and RKO/DDP cells using lipofectamineTM2000. The expression of lncRNA PVT1 in CRC tissues and cells was tested by Real-time qPCR. CCK-8 assay, flow cytometry and WB were performed to test the effect of PTV1 knockout or enforcement on cell proliferation, apoptosis and expressions of apoptosis-related proteins, respectively. The CRC subcutaneous transplanted xenograft model was established on athymic nude mice to study the effect of PVT1 over-expression on tumor growth and DDP resistance. Results: PVT1 was highly expressed in the cancer tissues and CRC cells, and its expression was positively associated with cisplatin resistance of CRC. After knockdown of PVT1, the proliferation of cisplatinresistant CRC cells was significantly suppressed, while the apoptosis was significantly enhanced (P<0.05 or P<0.01); Mechanically, the levels of drug resistance-associated molecules, including MDR1 and MRP1, as well as the expression of anti-apoptotic Bcl-2 were significantly downregulated whereas the levels of pro-apoptotic Bax and cleaved caspase-3 were increased in PVT1-silenced DDP-resistant CRC cells. Over-expression of PVT1 reversely increased proliferation and decreased apoptosis of CRC cells (P<0.05 or P<0.01). In addition, PVT1 over-expression in CRC cells significantly promoted DDP-resistance in vivo (P<0.05). Conclusion: Collectively, knockdown of PVT1 expression can significantly suppress cell proliferation and promote apoptosis of DDP-resistant CRC cells. Overexpression of PVT1 can significantly promote the growth of CRC cells in vitro and transplanted xenograft in vivo. PVT1 regulates endogenous apoptosis pathways and further promotes the sensitivity of CRC cells to cisplatin chemotherapy via inhibiting the expressions of MDR1 and MRP1.

Objective To investigate the incidence of serum monoclonal immunoglobulins (McIg) in B-cell chronic lymphoproliferative disorders (B-CLPD) and the clinical significance of McIg in B-CLPD and its possible sources.Methods A total of 1 147 patients with B-CLPD treated from May 2006 to May 2015 were enrolled into this retrospective study.The incidence of McIg and the relationship between McIg and prognostic factors in patients with B-CLPD were analyzed.Results Out of 1 147 B-CLPD patients,there were 164 patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM),and among them,McIg was detected in 140 cases (85.4 ％).In the remaining 983 patients with B-CLPD,monoclonal Ig was detected in 50 (5.1％) patients.Most of McIg in 2 groups were IgM paraprotein.The levels of IgM paraprotein of the LPL/WM group,non-LPL./WM group and McIg-negative patients were (48.88±33.42) g/L,(27.9±15.23) g/L and (2.75±1.21) g/L,respectively,the difference was statistical significance (P=0.000);the level of IgM paraprotein in LPL/WM group was significantly higher than that in non-LPL/WM group (P=0.000).The level of paraprotein decreased significantly when the patients got complete response after therapy (P=0.001,0.048,respectively).The incidence of serum McIg was higher in the group with complex karyotype (P =0.016) andwith high level of β2-microglobulin (β2-MG) (P =0.001).In the 47 non-LPL/WM patients with positive McIg,serum McIg in 38 (80.9 ％) patients were expressed in a pattern consistent with the distribution of tumor cells (P ＜ 0.005).Most of the light chain subtype of the McIg were consistent with the light chain subtype of the membrane immunoglobulin on the tumor cells.Conclusions Some non-LPL/WM B-CLPD patients also have serum McIg,and it could have certain relevance with the prognosis of B-CLPD.Moreover,the McIg may be secreted by tumor cells or those derived from the same progenitor cells with tumor cells.

BACKGROUND:Apexification and mineral trioxide aggregate apexification are mainly used to treat pulpal necrosis in the immature permanent tooth, but neither methods can increase the root canal length and thickness. How to promote the root development of the affected teeth based on patients' potential? Pulp regeneration and revascularization has provided a new direction for clinical treatment, but successful cases are rarely reported. OBJECTIVE: To testify the clinical effectiveness of pulp regeneration and revascularization in the treatment of pulpal necrosis, root development stagnation in the permanent teeth caused by caries, odontodysplasia and injury, thus providing reference for clinical application. METHODS:We propose to conduct a prospective, single-center, randomized, controlled, clinical trial at Stomatological Hospital Affiliated to Xi'an Jiaotong University, Shaanxi Province, China. Eighty-two patients (82 affected teeth) with pulpal necrosis or periapical periodontitis in the immature permanent tooth from December 2013 to December 2016 were selected, and equally randomized into trial and control groups, followed by treated with pulp regeneration and revascularization, and apexification, respectively. The clinical examinations and X-ray radiology were used to evaluate the clinical effectiveness at 3, 6, 9, 12 and 18 months, and the pulp vitality and rot development were observed. The study protocol has been approved by the Ethics Committee of Stomatological Hospital Affiliated to Xi'an Jiaotong University of China (approval number: JDKY015-02). All protocols were performed in accordance with the Ethical Principles for Medical Research Involving Human Subjects in theDeclaration of Helsinki. Written informed consent was provided by each patient and their family members after they indicated that they fully understood the treatment plan. RESULTS AND CONCLUSION: Up to March 25, 2017, all patients have been followed up for 6.5-18 months. The treatment success rate in the trial and control groups was 97.6% and 82.9%, respectively, and the intergroup difference was significant (P < 0.05). The positive rate of pulp vitality in the trial and control groups was 24.4% and 0, respectively, which showed significant difference (P < 0.05). The rate of root continuous development showed significant difference between trial and control groups (63.4%vs. 29.3%,P < 0.05). To conclude, compared with apexification, pulp regeneration and revascularization exhibits high success rate in the treatment of pulpal necrosis in the immature permanent tooth, and can contribute to root development.