BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

Gallbladder cancer constitutes the most prevalent malignant tumor of the biliary tract. It exhibits clinical characteristics such as challenging diagnosis in early stages, aggressive invasiveness, and poor prognosis. Studies have discovered that the occurrence, development, and metastasis of malignant tumors are closely associated with the inflammatory response, and the level of systemic inflammation within the body can be reflected by peripheral blood inflammatory indicators. This review delineates the research progress on the correlation between peripheral blood inflammatory markers and the prognosis of gallbladder cancer, with the intention of providing references for the diagnosis, treatment, and prognosis evaluation of gallbladder cancer.

Objective:To construct and verify a prognosis model of nomogram for the patients with locally advanced oral squamous cell carcinoma(OSCC).Methods:7 118 clinical cases with locally advanced OSCC from 2010 to 2015 in SEER database were in-cluded and randomly divided into training set(TS)and validation set(VS)by a 7:3 ratio.In TS,univariate and multivariate Cox proportional risk models were used to screen and determine the prognostic factors of locally advanced OSCC,and a nomogram predic-tion model was constructed to predict the cancer specific survival rate(CSS)of patients in 3 and 5 years.In TS and VS,the consis-tency index(C-index)and ROC curves were used to evaluate the differentiation of the model,the calibration curves were used to eval-uate the prediction accuracy of the model,and the decision curve analysis(DC A)method was used to evaluate the clinical applicabil-ity of the model.Results:4 984 and 2 134 cases were respectively included in TS and VS.No statistical difference of the analysis in-dexes was found between the 2 sets(P＞0.05).10 risk factors affecting the prognosis of the patients with locally advanced OSCC were identified in TS,including age,sex,race,marital status,location of onset,degree of histological differentiation,T stage,N stage,with or without operation and radiotherapy(P＜0.05).In the TS and VS,the C-index of the nomogram was 0.702 and 0.704 respectively,and the AUC of the 3-year and 5-year CSS was between 0.727 and 0.736.The calibra-tion curves showed that the 3-and 5-year CSS predicted by the nomogram model was in good agreement with the actual CSS.The DCA curves showed that the clinical benefit of the nomogram was better than that of the 7th e-dition of the AJCC TNM staging system.Conclusion:The nomogram constructed in this study can accurately predict the survival rate of OSCC patients with locally advanced tumor.

Objective To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts(HGFs)and to provide experimental evidence for surface modification of implant abutments.Methods The samples were divided into an NC group(negative control,no other treatment on a smooth surface),an NM-1 group(nanomesh-1,electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage),and an NM-2 group(nanomesh-2,electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage).The surface morpholo-gies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy(SEM).The surface hydrophilicities of the samples were measured with a contact angle measuring instrument.The prolif-eration of HGFs on the different samples were evaluated with CCK-8,and the expression of adhesion-related genes,in-cluding collagen Ⅰ(COL1A1),collagen Ⅲ(COL3A1),fibronectin 1(FN1),focal adhesion kinase(FAK),vinculin(VCL),integrin α2(ITGA2),and integrin β1(ITGB1),on the different samples was measured with qRT-PCR.The ex-pression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy(CLSM)after immuno-fluorescent staining.Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.Results SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups,with grid diameters of approximately 30 nm for the NM-1 group and approxi-mately 150 nm for the NM-2 group.Compared with that of the NC group,the water contact angles of the NM-1 group and NM-2 groups were significantly lower(P＜0.000 1).Cell proliferation in the NM-1 group was significantly greater than that in the NC group(P＜0.01).Moreover,there was no significant difference in the water contact angles or cell prolifer-ation between the NM-1 group and the NM-2 group.SEM revealed that HGFs were adhered well to the surfaces of all samples,while the HGFs in the NM-1 and NM-2 groups showed more extended areas,longer morphologies,and more de-veloped pseudopodia than did those in the NC group after 24 h.qRT-PCR revealed that the expression levels of the ad-hesion-related genes COL1A1,COL3A1,FN1,FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups(P＜0.01).The expression of vinculin protein in the NM-1 group was the highest,and the num-ber of focal adhesions was greatest in the NM-1 group(P＜0.01).The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers(P＜0.000 1).Conclusion The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion,proliferation,colla-gen fiber secretion and syntheses of HGFs,and electrochemical dealloying of Ti6Al4V with a grid diameter of approxi-mately 30 nm obviously promoted HGF formation.

Objective To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts(HGFs)and to provide experimental evidence for surface modification of implant abutments.Methods The samples were divided into an NC group(negative control,no other treatment on a smooth surface),an NM-1 group(nanomesh-1,electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage),and an NM-2 group(nanomesh-2,electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage).The surface morpholo-gies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy(SEM).The surface hydrophilicities of the samples were measured with a contact angle measuring instrument.The prolif-eration of HGFs on the different samples were evaluated with CCK-8,and the expression of adhesion-related genes,in-cluding collagen Ⅰ(COL1A1),collagen Ⅲ(COL3A1),fibronectin 1(FN1),focal adhesion kinase(FAK),vinculin(VCL),integrin α2(ITGA2),and integrin β1(ITGB1),on the different samples was measured with qRT-PCR.The ex-pression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy(CLSM)after immuno-fluorescent staining.Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.Results SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups,with grid diameters of approximately 30 nm for the NM-1 group and approxi-mately 150 nm for the NM-2 group.Compared with that of the NC group,the water contact angles of the NM-1 group and NM-2 groups were significantly lower(P＜0.000 1).Cell proliferation in the NM-1 group was significantly greater than that in the NC group(P＜0.01).Moreover,there was no significant difference in the water contact angles or cell prolifer-ation between the NM-1 group and the NM-2 group.SEM revealed that HGFs were adhered well to the surfaces of all samples,while the HGFs in the NM-1 and NM-2 groups showed more extended areas,longer morphologies,and more de-veloped pseudopodia than did those in the NC group after 24 h.qRT-PCR revealed that the expression levels of the ad-hesion-related genes COL1A1,COL3A1,FN1,FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups(P＜0.01).The expression of vinculin protein in the NM-1 group was the highest,and the num-ber of focal adhesions was greatest in the NM-1 group(P＜0.01).The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers(P＜0.000 1).Conclusion The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion,proliferation,colla-gen fiber secretion and syntheses of HGFs,and electrochemical dealloying of Ti6Al4V with a grid diameter of approxi-mately 30 nm obviously promoted HGF formation.

Objective To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts(HGFs)and to provide experimental evidence for surface modification of implant abutments.Methods The samples were divided into an NC group(negative control,no other treatment on a smooth surface),an NM-1 group(nanomesh-1,electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage),and an NM-2 group(nanomesh-2,electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage).The surface morpholo-gies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy(SEM).The surface hydrophilicities of the samples were measured with a contact angle measuring instrument.The prolif-eration of HGFs on the different samples were evaluated with CCK-8,and the expression of adhesion-related genes,in-cluding collagen Ⅰ(COL1A1),collagen Ⅲ(COL3A1),fibronectin 1(FN1),focal adhesion kinase(FAK),vinculin(VCL),integrin α2(ITGA2),and integrin β1(ITGB1),on the different samples was measured with qRT-PCR.The ex-pression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy(CLSM)after immuno-fluorescent staining.Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.Results SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups,with grid diameters of approximately 30 nm for the NM-1 group and approxi-mately 150 nm for the NM-2 group.Compared with that of the NC group,the water contact angles of the NM-1 group and NM-2 groups were significantly lower(P＜0.000 1).Cell proliferation in the NM-1 group was significantly greater than that in the NC group(P＜0.01).Moreover,there was no significant difference in the water contact angles or cell prolifer-ation between the NM-1 group and the NM-2 group.SEM revealed that HGFs were adhered well to the surfaces of all samples,while the HGFs in the NM-1 and NM-2 groups showed more extended areas,longer morphologies,and more de-veloped pseudopodia than did those in the NC group after 24 h.qRT-PCR revealed that the expression levels of the ad-hesion-related genes COL1A1,COL3A1,FN1,FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups(P＜0.01).The expression of vinculin protein in the NM-1 group was the highest,and the num-ber of focal adhesions was greatest in the NM-1 group(P＜0.01).The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers(P＜0.000 1).Conclusion The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion,proliferation,colla-gen fiber secretion and syntheses of HGFs,and electrochemical dealloying of Ti6Al4V with a grid diameter of approxi-mately 30 nm obviously promoted HGF formation.

Gastroesophageal reflux disease （GERD） is a gastrointestinal motility disorder characterized by the reflux of gastric contents into the esophagus， leading to symptoms such as acid reflux and heartburn. The incidence of GERD is closely associated with psychological disorders， including anxiety and depression. The brain-gut axis， serving as a mediator of the bidirectional connection between the brain and the gastrointestinal tract， plays a crucial role in the occurrence and development of GERD with anxiety and depression. Various therapeutic approaches， including compound Chinese medicine internal therapy （such as Pingchong jiangni decoction， Tiaozhong huashi decoction， etc.）， combination therapy of internal and external Chinese medicine （such as Lianzhi xiere decoction combined with acupoint application， acupuncture at the back segment of governor vessel plus Chinese medication of soothing the liver and gallbladder， etc.）， and combination therapy of internal Chinese and western medicine （including Jianpi shugan decoction combined with rabeprazole， rabeprazole combined with Jianzhong jiangni decoction， etc.）， have been shown to regulate brain-gut peptides， intestinal flora， inflammatory factors and gastrointestinal hormones， thereby effectively alleviating GERD symptoms， anxiety and depression， and enhancing patients’ quality of life.

Objective To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts(HGFs)and to provide experimental evidence for surface modification of implant abutments.Methods The samples were divided into an NC group(negative control,no other treatment on a smooth surface),an NM-1 group(nanomesh-1,electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage),and an NM-2 group(nanomesh-2,electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage).The surface morpholo-gies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy(SEM).The surface hydrophilicities of the samples were measured with a contact angle measuring instrument.The prolif-eration of HGFs on the different samples were evaluated with CCK-8,and the expression of adhesion-related genes,in-cluding collagen Ⅰ(COL1A1),collagen Ⅲ(COL3A1),fibronectin 1(FN1),focal adhesion kinase(FAK),vinculin(VCL),integrin α2(ITGA2),and integrin β1(ITGB1),on the different samples was measured with qRT-PCR.The ex-pression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy(CLSM)after immuno-fluorescent staining.Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.Results SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups,with grid diameters of approximately 30 nm for the NM-1 group and approxi-mately 150 nm for the NM-2 group.Compared with that of the NC group,the water contact angles of the NM-1 group and NM-2 groups were significantly lower(P＜0.000 1).Cell proliferation in the NM-1 group was significantly greater than that in the NC group(P＜0.01).Moreover,there was no significant difference in the water contact angles or cell prolifer-ation between the NM-1 group and the NM-2 group.SEM revealed that HGFs were adhered well to the surfaces of all samples,while the HGFs in the NM-1 and NM-2 groups showed more extended areas,longer morphologies,and more de-veloped pseudopodia than did those in the NC group after 24 h.qRT-PCR revealed that the expression levels of the ad-hesion-related genes COL1A1,COL3A1,FN1,FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups(P＜0.01).The expression of vinculin protein in the NM-1 group was the highest,and the num-ber of focal adhesions was greatest in the NM-1 group(P＜0.01).The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers(P＜0.000 1).Conclusion The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion,proliferation,colla-gen fiber secretion and syntheses of HGFs,and electrochemical dealloying of Ti6Al4V with a grid diameter of approxi-mately 30 nm obviously promoted HGF formation.

Acute pancreatitis （AP） is one of the most clinically common acute digestive disorders characterized by quick onset，rapid progression，severe condition，and high mortality. If the disease is not timely intervened in the early stage，it can develop into severe AP in the later stage，which damages the long-term quality of life and brings serious economic burden to patients and their families. However， the pathogenesis of this disease is complex and has not been fully explained. The generation and development of AP is closely related to many signaling pathways. Among them，Toll-like receptor 4（TLR4），as a transmembrane signal transduction receptor，can mediate immune response and inflammatory response，and play a key role in the occurrence and development of AP. Traditional Chinese medicine（TCM）can regulate the TLR4 signaling pathway with multiple targets，multiple effects，and multiple administration methods to inhibit inflammatory response，and effectively intervene in the progression of AP， which has gradually become a new craze for preventing and treating AP. Many studies have shown that TCM has obvious advantages in the prevention and treatment of AP. It can effectively treat AP by regulating TLR4 signaling pathway，strengthening immune resistance and defense，and inhibiting inflammatory response. Despite of the research progress，there is still a lack of comprehensive review on TCM regulation of TLR4 signaling pathway in the treatment of AP. Therefore，the literature on TCM regulation of TLR4 signaling pathway published in recent years was systematically reviewed and elaborated，aiming to provide new ideas for the treatment of AP and further drug development.

Objective To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts(HGFs)and to provide experimental evidence for surface modification of implant abutments.Methods The samples were divided into an NC group(negative control,no other treatment on a smooth surface),an NM-1 group(nanomesh-1,electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage),and an NM-2 group(nanomesh-2,electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage).The surface morpholo-gies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy(SEM).The surface hydrophilicities of the samples were measured with a contact angle measuring instrument.The prolif-eration of HGFs on the different samples were evaluated with CCK-8,and the expression of adhesion-related genes,in-cluding collagen Ⅰ(COL1A1),collagen Ⅲ(COL3A1),fibronectin 1(FN1),focal adhesion kinase(FAK),vinculin(VCL),integrin α2(ITGA2),and integrin β1(ITGB1),on the different samples was measured with qRT-PCR.The ex-pression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy(CLSM)after immuno-fluorescent staining.Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.Results SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups,with grid diameters of approximately 30 nm for the NM-1 group and approxi-mately 150 nm for the NM-2 group.Compared with that of the NC group,the water contact angles of the NM-1 group and NM-2 groups were significantly lower(P＜0.000 1).Cell proliferation in the NM-1 group was significantly greater than that in the NC group(P＜0.01).Moreover,there was no significant difference in the water contact angles or cell prolifer-ation between the NM-1 group and the NM-2 group.SEM revealed that HGFs were adhered well to the surfaces of all samples,while the HGFs in the NM-1 and NM-2 groups showed more extended areas,longer morphologies,and more de-veloped pseudopodia than did those in the NC group after 24 h.qRT-PCR revealed that the expression levels of the ad-hesion-related genes COL1A1,COL3A1,FN1,FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups(P＜0.01).The expression of vinculin protein in the NM-1 group was the highest,and the num-ber of focal adhesions was greatest in the NM-1 group(P＜0.01).The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers(P＜0.000 1).Conclusion The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion,proliferation,colla-gen fiber secretion and syntheses of HGFs,and electrochemical dealloying of Ti6Al4V with a grid diameter of approxi-mately 30 nm obviously promoted HGF formation.