BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To explore the clinical effect of endoscopic radical thyroidectomy via three-port gasless intermuscular approach.Methods:This is a retrospective cohort study. The data of 148 patients who underwent radical thyroidectomy at the Fourth General Surgery Department of the Second Affiliated Hospital of Harbin Medical University from January to June 2024 were retrospectively analyzed. There were 31 males and 117 females,aging (43.5±9.6) years (range: 21 to 64 years). The surgical method was selected according to the needs and wishes of patients. Among them, 77 cases underwent endoscopic radical thyroidectomy via unilateral three-port gasless intermuscular approach (three-port gasless group),and 71 cases underwent unilateral conventional open radical thyroidectomy(open group). The surgical technique exploration curve of the three-port gasless group was drawn based on the operation time and the number of lymph node dissections,and the technical exploration period and the technical maturity period were divided. The clinical data of the cases in the three-port gasless group and the open group were compared during the technical maturity period. The independent sample t test was used to compare the quantitative data between the two groups, and the χ2 test or Fisher exact probability method was used to compare the categorical data, respectively. Results:According to the technical exploration curve,there were 11 cases in the technical exploration period of the three-port gasless group,and 66 cases in the technical maturity period. In the technical mature period,the injury rate of temporary recurrent laryngeal nerve in the three-port gasless group was 1.5% (1/65),and the number of lymph node dissections was 5.9±3.5(range:0 to 14),which was not statistically significant compared with 4.4% (3/68) and 5.8±3.7(range:0 to 16) in the open group (all P>0.05). In the technical mature period,the operation time of the three-port gasless group was (39.2±6.2)minutes(range:30 to 55 minutes) and the postoperative drainage volume was (57.6±11.8) ml(range:30 to 90 ml),which were lower than those of the open group((67.8±13.9) minutes (range: 30 to 105 minutes) and (82.9±22.4)ml(range:50 to 175 ml)),and the differences were statistically significant ( t=15.303, 8.177, both P>0.05). During the technical maturity period,the postoperative hospital stay in the three-port gasless group was (3.2±0.4)days(range:3 to 4 days), which was not statistically different from that of the open group((3.2±0.4)days(range:3 to 5 days))( P>0.05). The incision satisfaction of patients in the three-port gasless group one month after the operation was higher than that of the control group (100% vs. 62.0%) ( P<0.01). Conclusion:Compared with open surgery,endoscopic radical thyroidectomy via three-port gasless intermuscular approach has certain advantages in terms of operation time, postoperative drainage volume and patient cosmetic satisfaction.

Objective:To investigate the management options for loop plate cutting of the tibial cortex during reconstruction of the anterior cruciate ligament (ACL) by the all-inside technique.Methods:From January 2022 to December 2024, a total of 13 patients with ACL injury who underwent all-inside reconstruction with tibial lateral loop plate cutting of the cortex and immediate revision for ACL injuries at Department of Sports Medicine, the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed (cut group). There were 5 males and 8 females with an average age of 28.7±9.1 years (range, 17-39 years). During the revision, a transverse tunnel was drilled at the distal end of the tibial tunnel, and the loop plate was fixed to the lateral tibial cortex through the transverse tunnel. Matched by gender, age, and side, the patients who underwent ACL reconstruction with all-inside loop steel without cutting the tibial cortex during the same period (the uncut group) were selected as the control group at a ratio of 1∶2, including 10 males and 16 females, aged 29.1±9.3 years (range, 17-39 years). The visual analogue scale (VAS), Tegner score, International Knee Documentation Committee (IKDC) and Lysholm score for knee pain before and after surgery were compared between the two groups, and bone tunnel enlargement was assessed using the Peyrache grading scale.Results:All patients were successfully operated and followed up for 13.1±2.5 months and 13.3±2.6 months, respectively. The Lysholm scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 35.44±15.69, 75.21±16.77, and 93.47±18.56 respectively, while those of the uncut group were 37.81±17.33, 71.45±15.82, and 91.05±19.54. The Lysholm scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the Lysholm scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the Lysholm scores between the two groups before and after surgery ( P>0.05). The IKDC scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 39.12±14.28, 69.52±15.36, and 84.24±17.91 respectively, while those of the uncut group were 37.46±11.55, 72.81±17.73, and 87.62±18.52. The IKDC scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the IKDC scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the IKDC scores between the two groups before and after surgery ( P>0.05). The Tegner scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 1.61±1.11, 3.59±1.66, and 5.59±1.79 respectively, while those of the non-cutting group were 1.57±1.05, 3.47±1.51, and 5.41±1.63. The Tegner scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the Tegner scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the Tegner scores between the two groups before and after surgery ( P>0.05). According to Peyrache's grading criteria, 7 cases in the cutting group had femoral side bone tunnel enlargement and 8 cases had tibial side bone tunnel enlargement; 12 cases in the non-cutting group had femoral side bone tunnel enlargement and 15 cases had tibial side bone tunnel enlargement, with no statistically significant differences (χ 2=0.205, P=0.650; χ 2=0.053, P=0.818). At the last follow-up, there were 2 cases of Lachman grade I in the cutting group and 3 cases in the non-cutting group, 1 case of joint stiffness in the cutting group and 2 cases in the non-cutting group. None of the patients in the two groups had vascular nerve injury, deep vein thrombosis, or intra-articular infection. Conclusion:The method of drilling a transverse tunnel at the distal end of the outer opening of the tibial tunnel and fixing the loop plate to the lateral tibial cortex through the transverse tunnel, along with cutting the tibial cortex, can improve the knee joint function.

Objective:To investigate the management options for loop plate cutting of the tibial cortex during reconstruction of the anterior cruciate ligament (ACL) by the all-inside technique.Methods:From January 2022 to December 2024, a total of 13 patients with ACL injury who underwent all-inside reconstruction with tibial lateral loop plate cutting of the cortex and immediate revision for ACL injuries at Department of Sports Medicine, the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed (cut group). There were 5 males and 8 females with an average age of 28.7±9.1 years (range, 17-39 years). During the revision, a transverse tunnel was drilled at the distal end of the tibial tunnel, and the loop plate was fixed to the lateral tibial cortex through the transverse tunnel. Matched by gender, age, and side, the patients who underwent ACL reconstruction with all-inside loop steel without cutting the tibial cortex during the same period (the uncut group) were selected as the control group at a ratio of 1∶2, including 10 males and 16 females, aged 29.1±9.3 years (range, 17-39 years). The visual analogue scale (VAS), Tegner score, International Knee Documentation Committee (IKDC) and Lysholm score for knee pain before and after surgery were compared between the two groups, and bone tunnel enlargement was assessed using the Peyrache grading scale.Results:All patients were successfully operated and followed up for 13.1±2.5 months and 13.3±2.6 months, respectively. The Lysholm scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 35.44±15.69, 75.21±16.77, and 93.47±18.56 respectively, while those of the uncut group were 37.81±17.33, 71.45±15.82, and 91.05±19.54. The Lysholm scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the Lysholm scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the Lysholm scores between the two groups before and after surgery ( P>0.05). The IKDC scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 39.12±14.28, 69.52±15.36, and 84.24±17.91 respectively, while those of the uncut group were 37.46±11.55, 72.81±17.73, and 87.62±18.52. The IKDC scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the IKDC scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the IKDC scores between the two groups before and after surgery ( P>0.05). The Tegner scores of the cutting group before surgery, 6 months after surgery, and 1 year after surgery were 1.61±1.11, 3.59±1.66, and 5.59±1.79 respectively, while those of the non-cutting group were 1.57±1.05, 3.47±1.51, and 5.41±1.63. The Tegner scores of both groups 6 months and 1 year after surgery were higher than those before surgery, and the Tegner scores 1 year after surgery were higher than those 6 months after surgery, with statistically significant differences ( P<0.05). There were no statistically significant differences in the Tegner scores between the two groups before and after surgery ( P>0.05). According to Peyrache's grading criteria, 7 cases in the cutting group had femoral side bone tunnel enlargement and 8 cases had tibial side bone tunnel enlargement; 12 cases in the non-cutting group had femoral side bone tunnel enlargement and 15 cases had tibial side bone tunnel enlargement, with no statistically significant differences (χ 2=0.205, P=0.650; χ 2=0.053, P=0.818). At the last follow-up, there were 2 cases of Lachman grade I in the cutting group and 3 cases in the non-cutting group, 1 case of joint stiffness in the cutting group and 2 cases in the non-cutting group. None of the patients in the two groups had vascular nerve injury, deep vein thrombosis, or intra-articular infection. Conclusion:The method of drilling a transverse tunnel at the distal end of the outer opening of the tibial tunnel and fixing the loop plate to the lateral tibial cortex through the transverse tunnel, along with cutting the tibial cortex, can improve the knee joint function.

Objective:To explore the clinical effect of endoscopic radical thyroidectomy via three-port gasless intermuscular approach.Methods:This is a retrospective cohort study. The data of 148 patients who underwent radical thyroidectomy at the Fourth General Surgery Department of the Second Affiliated Hospital of Harbin Medical University from January to June 2024 were retrospectively analyzed. There were 31 males and 117 females,aging (43.5±9.6) years (range: 21 to 64 years). The surgical method was selected according to the needs and wishes of patients. Among them, 77 cases underwent endoscopic radical thyroidectomy via unilateral three-port gasless intermuscular approach (three-port gasless group),and 71 cases underwent unilateral conventional open radical thyroidectomy(open group). The surgical technique exploration curve of the three-port gasless group was drawn based on the operation time and the number of lymph node dissections,and the technical exploration period and the technical maturity period were divided. The clinical data of the cases in the three-port gasless group and the open group were compared during the technical maturity period. The independent sample t test was used to compare the quantitative data between the two groups, and the χ2 test or Fisher exact probability method was used to compare the categorical data, respectively. Results:According to the technical exploration curve,there were 11 cases in the technical exploration period of the three-port gasless group,and 66 cases in the technical maturity period. In the technical mature period,the injury rate of temporary recurrent laryngeal nerve in the three-port gasless group was 1.5% (1/65),and the number of lymph node dissections was 5.9±3.5(range:0 to 14),which was not statistically significant compared with 4.4% (3/68) and 5.8±3.7(range:0 to 16) in the open group (all P>0.05). In the technical mature period,the operation time of the three-port gasless group was (39.2±6.2)minutes(range:30 to 55 minutes) and the postoperative drainage volume was (57.6±11.8) ml(range:30 to 90 ml),which were lower than those of the open group((67.8±13.9) minutes (range: 30 to 105 minutes) and (82.9±22.4)ml(range:50 to 175 ml)),and the differences were statistically significant ( t=15.303, 8.177, both P>0.05). During the technical maturity period,the postoperative hospital stay in the three-port gasless group was (3.2±0.4)days(range:3 to 4 days), which was not statistically different from that of the open group((3.2±0.4)days(range:3 to 5 days))( P>0.05). The incision satisfaction of patients in the three-port gasless group one month after the operation was higher than that of the control group (100% vs. 62.0%) ( P<0.01). Conclusion:Compared with open surgery,endoscopic radical thyroidectomy via three-port gasless intermuscular approach has certain advantages in terms of operation time, postoperative drainage volume and patient cosmetic satisfaction.

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Iron metabolism refers to the process of absorption,transport,excretion and storage of iron in organisms,including the biological activities of iron ions and iron-binding proteins in cells.Clinical research and animal experiments have shown that iron metabolism is associated with the progress of periodontitis.Iron metabolism not only enhances the proliferation and toxicity of periodontal pathogens,but also activate host immune-inflammatory response mediated by macrophages,neutrophils and lymphocytes.In addition,iron metabolism is also involved in regulating cellular death sensitivity of gingival fibroblasts and osteoblasts and promoting the differentiation of osteoclasts,which plays a regulatory role in the regeneration and repair of periodontal tissue.This article reviews the research progress on the pathogenesis of periodontitis from the perspective of iron metabolism,aiming to provide new ideas for the treatment of periodontitis.

Objective:To investigate the application effect of Press-Z-track-Turn (PZT) intramuscular injection on the extravasation, local reaction, local pain after injection and patient satisfaction after Fulvestrant injection.Methods:Used a self-controlled study, 63 patients who underwent bilateral intramuscular injection of Fluvastatin in the outpatient injection room of Tianjin Medical University Cancer Hospital from August to October 2022 were conveniently selected. The observation time was two treatment cycles after inclusion in this study. Before the injection of the first treatment cycle, a coin toss was used to randomly decide to use traditional intramuscular injection and PZT intramuscular injection method for injection and record. After 28 days, another injection method was used, with a total of 126 injections per injection method. Observed the extravasation of drug solution and local reactions at the injection site within 7 days after injection using two injection methods, as well as the pain and satisfaction of patients within 7 days after injection.Results:The extravasation rate of drug solution for the PZT intramuscular injection was 1.59% (2/126), which was lower than 7.14% (9/126) for the traditional intramuscular injection, and the difference was statistically significant ( χ2=4.66, P<0.05); the incidence of mild and moderate local reactions for the PZT intramuscular injection was 3.97% (5/126) and 1.59% (2/126), respectively, lower than that for the traditional intramuscular injection 11.11% (14/126) and 5.56% (7/126), and the difference was statistically significant ( χ2=8.26, P<0.05); the pain score of the PZT intramuscular injection was (2.08 ± 0.85) points, lower than that of the traditional intramuscular injection (5.03 ± 1.06) points, and the satisfaction score of the PZT intramuscular injection was (23.68 ± 1.64) points, higher than that of the traditional intramuscular injection (20.10 ± 2.58) points. The difference was statistically significant ( t=-17.24, 9.16, both P<0.01). Conclusions:PZT intramuscular injection can effectively reduce the overflow rate, the incidence of grade 1 and 2 local reactions and the degree of pain of patients, and improve patient satisfaction, which is worthy of clinical application.

Streptococcus mutans (S. mutans) is generally regarded as a major contributor to dental caries because of its ability to synthesize extracellular polysaccharides (EPS) that aid in the formation of plaque biofilm. The VicRKX system of S. mutans plays an important role in biofilm formation. The aim of this study was to investigate the effects of vicK gene on specific characteristics of EPS in S. mutans biofilm. We constructed single-species biofilms formed by different mutants of vicK gene. Production and distribution of EPS were detected through atomic force microscopy, scanning electron microscopy and confocal laser scanning microscopy. Microcosmic structures of EPS were analyzed by gel permeation chromatography and gas chromatography-mass spectrometry. Cariogenicity of the vicK mutant was assessed in a specific pathogen-free rat model. Transcriptional levels of cariogenicity-associated genes were confirmed by quantitative real-time polymerase chain reaction. The results showed that deletion of vicK gene suppressed biofilm formation as well as EPS production, and EPS were synthesized mostly around the cells. Molecular weight and monosaccharide components underwent evident alterations. Biofilms formed in vivo were sparse and contributed a decreased degree of caries. Moreover, expressional levels of genes related to EPS synthesis were down-regulated, except for gtfB. Our report demonstrates that vicK gene enhances biofilm formation and subsequent caries development. And this may due to its regulations on EPS metabolism, like synthesis or microcosmic features of EPS. This study suggests that vicK gene and EPS can be considered as promising targets to modulate dental caries.
Animals ; Biofilms ; Dental Caries ; Dental Plaque ; Rats ; Streptococcus mutans/genetics*