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.

Objective To evaluate the therapeutic efficacy of stenting combined with medication versus medication alone in treating severe extracranial carotid artery stenosis.Methods This prospective,multicenter cohort study enrolled 337 patients with carotid artery stenosis ranging from 70%to 99%.Based on patient preference,they were divided into two groups:a stent combined with medication group(antiplatelet drugs+statins,n=169)and a medication-only group(n=168).The study assessed perioperative safety and the incidence of recurrent cerebrovascular events related to the target vessel within one year.Results The success rate of the stent combined with medication group was 100%.There was one case of hyperperfusion-related intracranial hemorrhage during the perioperative period(1/169)The patient recovered well after medical treatment.There was no statistically significant difference in perioperative complications between the two groups(P=0.318).During the 1-year follow-up,the stent combined with medication group(3/169)had a significantly lower incidence of recurrent ischemic stroke compared to the medication-only group(15/168),with a statistically significant difference(P=0.003).Univariate analysis showed that gender(χ2=4.372,P=0.037),stenosis rate≥85%(χ2=10.738,P=0.001),and non-stent treatment(χ2=7.171,P=0.007)were risk factors for recurrent stroke.However,the number of recurrent ischemic strokes in females was relatively small and after adjusting the chi-square test,the difference was not statistically significant(P=0.075).Logistic regression analysis revealed that stenosis rate≥85%(OR=115.925,95%CI:2.077-122.102,P=0.008)and non-stent treatment(OR=0.158,95%CI:0.044-0.564,P=0.004)were independent risk factors for recurrent cerebrovascular events within one year.Conclusions In patients with≥85%extracranial carotid artery stenosis,stenting combined with medication reduces recurrent ischemic cerebrovascular events within 1 year.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

To characterize the genomes of different emm-type group A Streptococcus (GAS), their virulence genes and drug resistance profiles in Tianjin City from 2011 to 2024. After PCR, a total of 42 strains with different years and emm types were selected for whole genome sequencing and multi-locus sequence typing (MLST), and the core genomes were used to generate a phylogenetic tree, after which the virulence genes and resistance genes were identified and analyzed, followed by the drug susceptibility test. In this study, the GAS strains were dominated by emm1 (50.0%) and emm12 (40.4%), and the MLST phenotypes were categorized into six types: ST36 (40.4%), ST1274 (26.1%), ST28 (23.8%), ST921 (4.7%), ST46 (2.3%), and ST403 (2.3%). There was a high consistency between their emm-types and ST types. A total of 68 virulence genes were detected in the genomes of 42 GAS strains, involving functional genes encoding exotoxin, bacterial adhesion, extracellular enzymes, etc. The virulence genes they carried were significantly different between emm1-type and emm12-type strains, such as speA. At the same time, the carrying rates of some virulence genes in the same emm-type strains changed with time, such as hyl. The resistance genes were basically the same among different emm-type strains except for the vanSE gene detected in all emm12 strains. The results of drug sensitivity showed that the GAS strains isolated in Tianjin City from 2011 to 2024 were sensitive to penicillin, cefazolin, chloramphenicol, vancomycin, and levofloxacin, while the resistance rates to erythromycin, azithromycin, clarithromycin, and clindamycin ranged from 88.5% to 100.0%, and there was a certain degree of consistency between the resistance phenotypes and the detected resistance genes. Overall, the main emm types and evolutionary features of GAS in Tianjin City from 2011 to 2024 were consistent with the dominant types in China, and the carrying rate of virulence genes and drug resistance genes differed significantly among different emm-type strains, and there were continuous evolution and variation in the prevalence of virulence genes in GAS.

BACKGROUND:Vital pulp therapy is one of the main treatments for common oral diseases such as deep caries.The antibacterial properties of pulp-capping materials are crucial to the efficacy of the treatment.Currently,commonly used pulp-capping material has weak antibacterial properties and may induce a certain degree of inflammatory response in the pulp tissue,leading to treatment failure.OBJECTIVE:To investigate the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin@Gap19(AgNPs-rGO/PDA/GelMA@Gap19)hydrogel material.METHODS:Nanosilver-reduced graphene oxide was prepared.Human dental pulp stem cells were cultured in complete medium containing different mass concentrations of nanosilver-reduced graphene oxide.Cell proliferation was detected by CCK-8 assay.The inhibition zone assay was used to detect the inhibitory effect of different mass concentrations of nanosilver-reduced graphene oxide on Staphylococcus aureus.The nanosilver-reduced graphene oxide mass concentration with the most obvious cell proliferation and antibacterial effects was screened by the results of CCK-8 and inhibition zone assays,and loaded into hydrogels.Human dental pulp stem cells were cultured in complete medium containing different concentrations of Gap19(a specific inhibitor of connexin 43 hemichannels),and cell proliferation was detected by CCK-8 assay.The Gap19 concentration with the most obvious cell proliferation effect was screened and loaded into hydrogels.AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was prepared,and the physicochemical properties of the hydrogel material were characterized.The suspension of Staphylococcus aureus(or Escherichia coli,Streptococcus mutans,Lactobacillus)was co-cultured with mineral trioxide aggregates,polydopamine/methacrylated gelatin hydrogel,nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel.The bacterial suspension cultured alone was used as the blank control group to detect the antibacterial rate of each group of hydrogels.RESULTS AND CONCLUSION:(1)The optimal mass concentration of nanosilver-reduced graphene oxide was determined to be 12.5 μg/mL by CCK-8 assay and inhibition zone test results,and the optimal concentration of Gap19 was determined to be 20 μmol/L by CCK-8 assay.(2)Scanning electron microscopy showed that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was wrinkled and porous,and nanosilver was loaded on the surface and inside of the hydrogel.Energy spectrum analysis results showed that nanosilver-reduced graphene oxide and Gap19 were successfully loaded on the hydrogel.(3)The four hydrogels had obvious inhibitory effects on Staphylococcus aureus,Escherichia coli,Streptococcus mutans,and Lactobacillus,and the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacryloyl gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel were the most significant,indicating that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel,as a new type of pulp capping material,has an obvious antibacterial effect.

BACKGROUND:Vital pulp therapy is one of the main treatments for common oral diseases such as deep caries.The antibacterial properties of pulp-capping materials are crucial to the efficacy of the treatment.Currently,commonly used pulp-capping material has weak antibacterial properties and may induce a certain degree of inflammatory response in the pulp tissue,leading to treatment failure.OBJECTIVE:To investigate the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin@Gap19(AgNPs-rGO/PDA/GelMA@Gap19)hydrogel material.METHODS:Nanosilver-reduced graphene oxide was prepared.Human dental pulp stem cells were cultured in complete medium containing different mass concentrations of nanosilver-reduced graphene oxide.Cell proliferation was detected by CCK-8 assay.The inhibition zone assay was used to detect the inhibitory effect of different mass concentrations of nanosilver-reduced graphene oxide on Staphylococcus aureus.The nanosilver-reduced graphene oxide mass concentration with the most obvious cell proliferation and antibacterial effects was screened by the results of CCK-8 and inhibition zone assays,and loaded into hydrogels.Human dental pulp stem cells were cultured in complete medium containing different concentrations of Gap19(a specific inhibitor of connexin 43 hemichannels),and cell proliferation was detected by CCK-8 assay.The Gap19 concentration with the most obvious cell proliferation effect was screened and loaded into hydrogels.AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was prepared,and the physicochemical properties of the hydrogel material were characterized.The suspension of Staphylococcus aureus(or Escherichia coli,Streptococcus mutans,Lactobacillus)was co-cultured with mineral trioxide aggregates,polydopamine/methacrylated gelatin hydrogel,nanosilver-reduced graphene oxide/polydopamine/methacrylated gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel.The bacterial suspension cultured alone was used as the blank control group to detect the antibacterial rate of each group of hydrogels.RESULTS AND CONCLUSION:(1)The optimal mass concentration of nanosilver-reduced graphene oxide was determined to be 12.5 μg/mL by CCK-8 assay and inhibition zone test results,and the optimal concentration of Gap19 was determined to be 20 μmol/L by CCK-8 assay.(2)Scanning electron microscopy showed that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel was wrinkled and porous,and nanosilver was loaded on the surface and inside of the hydrogel.Energy spectrum analysis results showed that nanosilver-reduced graphene oxide and Gap19 were successfully loaded on the hydrogel.(3)The four hydrogels had obvious inhibitory effects on Staphylococcus aureus,Escherichia coli,Streptococcus mutans,and Lactobacillus,and the antibacterial effects of nanosilver-reduced graphene oxide/polydopamine/methacryloyl gelatin hydrogel and AgNPs-rGO/PDA/GelMA@Gap19 hydrogel were the most significant,indicating that AgNPs-rGO/PDA/GelMA@Gap19 hydrogel,as a new type of pulp capping material,has an obvious antibacterial effect.

Objective:To compare the clinical effect of femoral neck system (FNS) and cannulated compression screw internal fixation in the treatment of femoral neck fractures in young and middle-aged patients.Methods:The databases of CNKI, Wanfang Data Knowledge Service Platform, VIP, Chinese Medical Journal Full-text Database, PubMed, Embase, Web of Science and Cochrane Library were searched. The intraoperative blood loss, intraoperative fluoroscopy times, hospital stay, fracture healing time, Harris hip function score, partial weight-bearing time and complication rate were extracted to compare the clinical efficacy of the two surgical methods. Stata18.0 statistical software was used for meta-analysis.Results:A total of 699 patients from 11 studies were included in this study. Compared with cannulated compression screw internal fixation, the FNS had a shorter operation time [ WMD= -8.54, 95% CI(-14.87, -2.21), P=0.008], fewer intraoperative fluoroscopy times[ WMD= -8.29, 95% CI(-11.45, -5.12), P< 0.001], a shorter fracture healing time [ WMD=-1.59, 95% CI(-2.49, -0.68), P=0.001], a shorter partial weight-bearing time[ WMD=-3.45, 95% CI(-4.43, -2.46), P<0.001], a lower incidence of postoperative complications [ RR=0.41, 95% CI(0.22, 0.76), P= 0.004], and a lower incidence of postoperative nonunion [ RR=0.40, 95% CI(0.18, 0.88), P=0.022]. Meanwhile, the FNS group had more intraoperative blood loss [ WMD=9.53, 95% CI(2.70, 16.35), P=0.006] and a higher Harris hip function score at the last follow-up [ WMD=3.50, 95% CI(2.11, 4.89), P<0.001] than the cannulated compression screw internal fixation group. There were no statistically significant differences in the length of hospital stay [ WMD=-0.48, 95% CI(-0.82, -0.13), P=0.092] or the incidence of femoral head necrosis [ RR=0.57, 95% CI(0.26, 1.24), P=0.159] between the two groups. Conclusion:Compared with cannulated compression screw internal fixation in the treatment of femoral neck fracture in young and middle-aged patients, FNS has more intraoperative blood loss, but it has more advantages in operation time, intraoperative blood loss, intraoperative fluoroscopy times, postoperative fracture healing time, Harris hip function score, partial weight-bearing time, postoperative nonunion rate and postoperative complications rate.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.

Objective To evaluate the therapeutic efficacy of stenting combined with medication versus medication alone in treating severe extracranial carotid artery stenosis.Methods This prospective,multicenter cohort study enrolled 337 patients with carotid artery stenosis ranging from 70%to 99%.Based on patient preference,they were divided into two groups:a stent combined with medication group(antiplatelet drugs+statins,n=169)and a medication-only group(n=168).The study assessed perioperative safety and the incidence of recurrent cerebrovascular events related to the target vessel within one year.Results The success rate of the stent combined with medication group was 100%.There was one case of hyperperfusion-related intracranial hemorrhage during the perioperative period(1/169)The patient recovered well after medical treatment.There was no statistically significant difference in perioperative complications between the two groups(P=0.318).During the 1-year follow-up,the stent combined with medication group(3/169)had a significantly lower incidence of recurrent ischemic stroke compared to the medication-only group(15/168),with a statistically significant difference(P=0.003).Univariate analysis showed that gender(χ2=4.372,P=0.037),stenosis rate≥85%(χ2=10.738,P=0.001),and non-stent treatment(χ2=7.171,P=0.007)were risk factors for recurrent stroke.However,the number of recurrent ischemic strokes in females was relatively small and after adjusting the chi-square test,the difference was not statistically significant(P=0.075).Logistic regression analysis revealed that stenosis rate≥85%(OR=115.925,95%CI:2.077-122.102,P=0.008)and non-stent treatment(OR=0.158,95%CI:0.044-0.564,P=0.004)were independent risk factors for recurrent cerebrovascular events within one year.Conclusions In patients with≥85%extracranial carotid artery stenosis,stenting combined with medication reduces recurrent ischemic cerebrovascular events within 1 year.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.