BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

BACKGROUND:Pure titanium and titanium alloy implants are widely used in the field of implant restoration due to their excellent biocompatibility and elastic modulus.However,the biological inertness of the surface of titanium-based implants leads to poor integration with surrounding bone tissues,and surface modification is required to improve the bone integration ability of titanium-based implants.OBJECTIVE:To fabricate hydroxyapatite/graphene oxide/interleukin-4 composite coatings on pure titanium substrates,and to investigate their physicochemical properties and biocompatibility of the coating materials.METHODS:Hydroxyapatite/graphene oxide/interleukin-4 composite coatings were prepared on pure titanium substrates by electrochemical deposition and freeze-drying.Titanium sheets loaded with interleukin-4 and titanium sheets loaded with hydroxyapatite/graphene oxide coatings were prepared at the same time,and the physicochemical properties of pure titanium sheets and the above three titanium sheets were characterized.MC3T3-E1 cells were inoculated on the surfaces of pure titanium sheets and the above three titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell activity was detected by Calcein-AM/PI staining.Cell morphology and adhesion were observed by scanning electron microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscopy,energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy,X-ray diffraction,and Raman spectroscopy confirmed the successful fabrication of the hydroxyapatite/graphene oxide/interleukin-4 composite coating on the titanium surface.The water contact angle of hydroxyapatite/graphene oxide/interleukin-4 group was larger than that of pure titanium group and hydroxyapatite/graphene oxide group,and smaller than that of interleukin-4 group.(2)CCK-8 assay and DAPI staining results showed that hydroxyapatite/graphene oxide/interleukin-4 coating could promote the proliferation of MC3T3-E1 cells.Calcein-AM/PI staining results showed that MC3T3-E1 cells in hydroxyapatite/graphene oxide/interleukin-4 coating group had higher activity and fewer dead cells.Scanning electron microscopy showed that MC3T3-E1 cells adhered to the surfaces of the four groups of materials with good cell morphology.Compared with the pure titanium group,the MC3T3-E1 cells in the interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger;compared with the hydroxyapatite/graphene oxide group,the MC3T3-E1 cells in the hydroxyapatite/graphene oxide/interleukin-4 group extended more pseudopodia,the cell-cell connections were closer,and the adhesion area was larger.(3)These findings indicate that the hydroxyapatite/graphene oxide/interleukin-4 composite coating possesses favorable physicochemical and biological properties.

Sepsis remains a challenge in critical care worldwide，with intestinal microbiome dysbiosis implicated in its onset，progression，and organ dysfunction. Germ-free （GF） and human microbiota-colonized animals，by eliminating confounding from resident microbiota and combining induction methods such as CLP/LPS/live-bacterial challenge with fecal microbiota transplantation （FMT） and mono- or combined colonization，enable causal tests and dissection of microbiota-host interactions and drug mechanisms. This review summarizes the application of GF and related models in sepsis research. At the immune level，TLR-related signaling and pathogen community-induced suppression of IRF3-dependent defense affect innate immunity and pathogen clearance. At the barrier level，reprogramming of tight junction proteins and increased permeability drive gut-derived amplification. At the metabolic level，short-chain fatty acids and bile acids function as metabolic valves influencing GPR/HDAC signaling. At the epigenetic level，EZH2 and histone deacetylation emerge as druggable targets. We further synthesize anti-sepsis evidence for traditional Chinese medicine （TCM），mainly from conventional animals and clinical studies，discussing how formulae （e.g.，Xuebijing，Shenfu，and Huanglian Jiedu Tang） and active constituents （e.g.，berberine，luteolin，ginsenosides，and resveratrol） may act through microbiota-related and direct host pathways，with FMT/metabolite replenishment enabling further causal testing. Finally，we propose a closed-loop GF-humanized-clinical stratification paradigm for integrated evaluation of microecology，epigenetics，immunity，and organ outcomes，providing a translational path for precision prevention and treatment based on TCM and the microbiome.

Objective To investigate the correlation between the drug resistance of Helicobacter pylori (H .pylori )and clinical eradication efficacy of bismuth-based quadruple therapies,and to guide clinical rational drug use in the region.Methods A total of 260 patients with H .pylori infections were collected.H .pylori from biopsied gastric mucosa tissues were isolated and cultured.Drug resistant rates of isolated H .pylori to metronidazole,clarithromycin,amoxicillin,levofloxacin and furanzolidone were tested.Patients were randomly divided into clarithromycin,levofloxacin,furanzolidone and metronidazole groups by completely randomized design.All patients received bismuth potassium 220 mg,esomeprazole 20 mg and amoxicillin 1 000 mg twice daily,and according to group received clarithromycin 500 mg, levofloxacin 200 mg,furanzolidone 100 mg and metronidazole 400 mg,twice daily,espectively.The treatment course was 10 days.At least four weeks after treatment,13 Curea breath test or 14 Curea breath test was taken.According to the intention to treat (ITT)and per-protocal (PP),the eradication rate of each group was caculated.Chi square test was performed to compare the differences between groups. Results The drug resistant rate of H .pylori to metronidazole,clarithromycin,amoxicillin,levofloxacin and furanzolidone was 94.2% (146/155 ), 21 .3% (33/155 ), 2.6% (4/155 ), 5 .8% (9/155 ) and 1 .9%(3/155),respectively.According to ITT analysis,the eradication rate of clarithromycin group, levofloxacin group,furanzolidone group and metronidazole group was 81 .5 %(53/65 ),90.8%(59/65 ), 93.8% (61/65 )and 75 .4%(49/65),respectively.And according to PP analysis which was 84.1 %(53/63),92.2%(59/64),95 .3%(61/64)and 79.0%(49/62 ),respectively.The differences between furanzolidone group and metronidazole group,clarithromycin group were staistcally significant (χ2ITT =8.509 and 4.561 ;χ2PP = 7.592 and 4.323,all P < 0.05 ).There was no statistical significance in the H .pylori eradication rate between resistant strains and sensitive strains of each group.Conclusion Bismuth-based quadruple therapy can overcome antibiotic resistance,the eradication rate of protocal with furanzolidone is higher and with good safety,which can be the first-line treatment for H .pylori eradication.

Objective To investigate effect of dexmedetomidine on postoperative analgesia pump dose and effect.Methods 50 cases of patients with abdominal surgery under general anesthesia were selected.According to the postoperative analgesic drugs were divided into control group and experimental group, 25 cases in each group were given corresponding drug treatment.After treatment, the visual analogue scale, comfort score, adverse reaction rate and dosage of analgesic drugs were detected and compared.Results Compared with the control group,the VAS score were lower(P <0.05),the BCS score were higher(P<0.05),the adverse reaction rate were lower(P<0.05),the dosage of analgesic pump were lower(P<0.05). Conclusion Dexmedetomidine can significantly reduce postoperative pain degree of patients, reduce the incidence of adverse reaction, reduce analgesic dosage of the drug pump.

Objective To evaluate the efficacy and safety of different bismuth-based quadruple therapies for Helicobacter pylori (H.pylori) eradication.Methods From December 2012 to October 2013,240 patients with H.pylori infection were collected and evenly divided into clarithromycin group,levofloxacin group,furanzolidone group and metronidazole group.Each group received bismuth potassium citrate 220 mg,esomeprazole 20 mg and amoxicillin 1 000 mg twice daily.In addition,each group received clarithromycin 500 mg,levofloxacin 200 mg,furanzolidone 100 mg,and metronidazole 400 mg,respectively.The course of treatment was 10 days.At least four weeks after the end of therapy and withdrawal the medicine,patients underwent fasting 13C-urea breath test or 14C-urea breath test.The negative result indicated as successful H.pylori eradication.The adverse effects were observed and recorded during treatment.The rate of H.pylori eradication was analyzed by the intention to treat (ITT) analysis and per protocol (PP) analysis.Chi-square test was performed for eradication rate comparison among groups.Results According to ITT analysis,the eradication rate of clarithromycin group,levofloxacin group,furanzolidone group and metronidazole group was 81.67％ (49/60),88.33％ (53/60),93.33％ (56/60) and 73.33％ (44/60),respectively,and according to PP analysis which was 85.96％ (49/57),89.83％ (53/59),94.92％ (56/59) and 75.86％ (44/58),respectively.The differences among four groups were statistically significant (x2 ＝10.13 and 9.89,both P＜0.05).The differences between furanzolidone group and metronidazole group were statistically significant (x2 =8.64 and 8.55,both P＜0.01).There were no statisticaly significant differences in adverse effects among the four groups (x2 =0.47,P＞0.05).Conclusion The H.pylori eradication rate is high in furanzolidone contained bismuth based quadruple therapy and with good safety,which could be the first line treatment for H.pylori eradication.