Objective: To examine effects of Platycodon grandiflorum (JG), Glycyrrhiza uralensis Fisch (GC) or the compound of JG with GC on the growth of cariogenic and periodontopathic bacteria in vitro . Methods: JG,GC and the compound were extracted with ?=65% ethanol respectively. The minimal inhibitory concentration(MIC)and minimal bactericidal concentration (MBC) of JG, GC or compound against S.mutans MT818, S. sobrinus 6715, P.gingivalis 381 and B.forsythus 43037 were measured by drug sensetivity test.Results: JG showed no effect on the growth of oral pathogens tested;GC inhibited S.mutans MT 8418 and S.sobrinus 6715 with MIC of 3.91 mg/ml.The compound inhibited the microorganisms with the MIC of 1.96 mg/ml against S.mutans MT8148 or S.sobrinus 6715, 3.91 mg/ml against P.gingivalis 381, 7.81 mg/ml against B.forsythus 43037 respectively.Conclusion: The compound of JG and GC has stronger inhibition and bactericidal effects on oral pathogens than the single medicine.

Objective To investigate the effect of total knee arthroplasty ( TKA) following high tibial osteotomy ( HTO) and to analyze the factors that may influence the operation .Methods A total of 16 patients (19 knees) who had undergone a previous HTO were treated with TKA between 2000 and 2010.The American Knee Society Scores ( KSS), femorotibial angle ,quadriceps angle ,posterior slope angle of tibial plateau ,Insall Salvatti Ratio and knee range of motion ( ROM) were evaluated for each patient pre-and post-operatively and the results were evaluated .Results The KSS scores improved from 73.20 ±3.56 scores preoperatively to 153.00 ±3.39 scores postoperatively (P <0.05).The femorotibial angle was corrected from 160.57°±3.30°preoperatively to 169.85°±1.34°postoperatively(P<0.05).The quadriceps angle was corrected from 24.57°±2.07°preoperatively to 17.28°±1.11°postoperatively (P<0.05).The posterior slope angle of tibial plateau was corrected from 2.25°±0.50°preoperatively to 3.75°±0.95°postoperatively (P<0.05).The Insall Salvatti Ratio improved from 0.80 ±0.08 preoperatively to 1.05 ±0.12 postoperatively ( P <0.05).The knee ROM improved to 38.25°±8.88°postoperatively from 96.25°±4.34°preoperatively(P<0.05).Conclusion TKA following HTO demands adequate soft tissue balancing , good limb alignment and appropriate prosthesis .

Objective To investigate the methods and effectiveness of heterotopic reconstruetion of hepatic artery in orthotopic liver transplantation. Methods The methods of heterotopic hepatic artery reconstruction and postoperative management of 36 cases of recipient vascular anomalies among 440 cases of liver transplantation performed in our hospital over a ten year period,were retospectively analysed. Results In 10 of 36 recipients the donor hepatic artery was anastomosed to recipient infrarenal aorta ,10 to the suprarenal aorta ,4 to the left gastric artery and 2 to the splenic artery. Five patients died perioperatively with patency of hepatic artery, and 31 recipients have survived for 3 to 48 months without hepatic artery complications; 1 patient had to receive liver retransplantation because of ischemic necrosis of bile duct. Conclusions In cases of disease or anomaly of recipient hepatic artery during liver transplantation,the heterotopic reconstruction of donor hepatic artery to the infarenal or suprarenal aorta,splenic artery or left gastric artery of the reeipient is indicated,and the results are satisfactory.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

OBJECTIVES: To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity. METHODS: C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice. RESULTS: In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice. CONCLUSIONS Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.
Male ; Humans ; Animals ; Mice ; Reactive Oxygen Species/metabolism* ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Mice, Inbred C57BL ; Apoptosis ; Poly(ADP-ribose) Polymerases/metabolism*

By analyzing the shift of microbial communities under different iron/sulfur ratios, the response of metallurgical microorganisms to energy substrates was investigated based on molecular ecological networks. High-throughput sequencing of microbial samples from different domesticated batches was conducted to analyze the changes in community composition, alpha and beta diversity. Based on the molecular ecological network, the interactions between microorganisms under different iron/sulfur ratios were explored. Keystones were identified to analyze the community response to energy substrates. In the process of domestication based on different energy substrates, the dominant species in the in iron-rich and sulfur-less community were Acidithiobacillus ferrooxidans and A. ferriphilus. A. thiooxidans accounted for up to 90% in the sulfur-rich and iron-less community after 3 domesticating batches. The results of alpha and beta diversity analysis show that the domestication process of sulfur-rich and iron-less substrates reduced the diversity of microbial communities. Molecular ecological network analysis shows that the keystones were all rare species with low abundance. During the domestication by sulfur-rich and iron-less energy substrates, the bacterial species had a closer symbiotic relationship and the community was more stable. Through this domestication experiment, the impact of different energy substrates on microbial aggregation was clarified. Domesticating metallurgical microorganisms by using sulfur-rich and iron-less energy substrates made the microbial colonies to be more stable, which was conducive to the oxidation of iron and sulfur, promoting the dissolution of sulfide minerals. Our findings provide a reference for the directional domestication of metallurgical microorganisms.
Acidithiobacillus/genetics* ; Iron ; Minerals ; Oxidation-Reduction ; Sulfur

To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU.

METHODSDrug-resistance gastric cancer cell line (SGC-7901/5-FU) was established by high doses of repeated impact joint drug concentration increment methods. The cell viability of the parent cell line and the drug-resistance cell line were determined by standard MTT assay. Cell survival rate of drug-resistance was calculated by the formula [(Aof the treatment group / Aof the control group) × 100%]. Cell half inhibitory concentration (IC) and resistance index (RI) were calculated by the Graphpad prime 6.0 software(RI=ICvalue of drug-resistance cells / ICvalue of parent cells). The apoptosis rate of SGC-7901/5-FU cells was quantified by flow cytometry after staining with annexin-V and PI. Western blot was used to detect the protein expression of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) and apoptosis-related proteins (PARP, Survivin, Bax and bcl-2).

RESULTSICvalue was significantly increased in drug-resistant cells compared with parental cells [(64.7±3.9) mg/L and (4.1±0.3) mg/L, respectively, t=26.46, P=0.000], and the RI was 15.6. Proliferation activity in the drug-resistant cells was higher than that in parental cells at different 5-FU concentrations (all P<0.05). In drug-resistant cells, the ICvalue of 5-FU combined with EGCG group obviously decreased compared with 5-FU group [(7.3±0.1) mg/L and (63.1±1.4) mg/L respectively, t=40.84, P=0.000], and the RI was 0.12. Proliferation activity in drug-resistant cells was significantly decreased after EGCG treatment at different 5-FU concentrations (all P<0.05). Cell apoptosis rates in control group, 5-FU group, EGCG group and 5-FU combined with EGCG group were (3.0±1.0)%, (7.0±1.3)%, (6.0±1.2)% and (18.0±1.4)%, while apoptosis rate in 5-FU combined with EGCG group was significantly higher than those of other 3 groups(F=129.5, P=0.000). Western blot revealed that after EGCG treatment, the expression levels of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) in the drug-resistant cell line SGC-7901/5-FU decreased significantly; the expression levels of apoptosis marker protein PARP and pro-apoptotic protein Bax increased significantly; and the expression levels of anti-apoptotic protein Survivin and Bcl-2 decreased significantly (all P<0.05).

CONCLUSIONEGCG can reduce the resistance of gastric cancer resistant cell line SGC-7901/5-FU, whose role may be via the inhibition of the expression of drug-resistance-related proteins, and the elevation of the protein expression ratio of PARP/Survivin and Bax/Bcl-2.

Anticarcinogenic Agents ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein