Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg^-1·d^-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D^*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm³ and (174.24±28.27)mm^3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P<0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P>0.05). The D^* values of the rhES group were (10.940±2.834)×10^-3mm²/s and (12.940±2.801)×10^-3mm²/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10^-3mm²/s and (7.898±1.603)×10^-3mm²/s of control group (P<0.05). Moreover, compared with control group, the D^* value of rhES group was significantly lower in day 12 (6.848±1.460)×10^-3mm²/s vs (9.950±2.596)×10^-3mm²/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D^* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D^* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

OBJECTIVE： To establish a method for simultaneous determination of gallic acid， cinnamic acid and catechin in 3 processed products of Rheum officinale. METHODS： RP-HPLC method was established. The determination was performed on Thermo ScientificTM Hypersil GOLD Dim column with mobile phase consisted of methanol-0.1％ phosphoric acid solution （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 278 nm， and the column temperature was 30 ℃. The sample size was 10 μL. RESULTS： The linear range of gallic acid， cinnamic acid and catechin were 0.126 2-1.262 0 μg（r＝0.999 9）， 0.036 2-0.362 0  μg（r＝0.999 9） and 0.177 9-1.779 4 μg（r＝0.999 8）， respectively. Quantitative limits were 25.4， 28.2， 62.5 ng， and detection limits were 6.2， 3.6， 11.8 ng， respectively. RSDs of precision， stability， repeatability and durability tests were all less than 3％. The recoveries ranged from 94.64％-102.71％（RSD＝2.74％， n＝9）， 95.35％-102.49％（RSD＝2.44％， n＝9）， 93.56％-103.66％（RSD＝3.27％， n＝9）. The determination results showed that the contents of gallic acid and cinnamic acid in prepared R. officinale were higher， and the order of both were prepared R. officinale＞steamed R. officinale＞raw R. officinale. The content of catechin in raw R. officinale was higher， and the order of it was raw R. officinale＞ steamed R. officinale＞prepared R. officinale. CONCLUSIONS： The method is sensitive， reliable and reproducible. It can be used to determine the contents of gallic acid， cinnamic acid and catechins in 3 processed products of R. officinale simultaneously.

Objective To analyze the effect of extralateral approach interbody fusion in the treatment of degenerative lumbar diseases. Methods A total of 50 patients with lumbar degenerative diseases admitted to our hospital were selected, and were treated with extralateral approach interbody fusion, and the therapeutic effect was observed and analyzed. Results All patients successfully completed the operation. The average amount of bleeding during operation was (145. 5 ± 4. 7) m L, the average operation time was (56. 3 ± 2. 2) min, and the average hospitalization time was (7. 2 ± 1. 5) days. Four patients suffered from hip flexion weakness after operation, and the symptoms recovered completely after two months. Six patients suffered from sensory numbness in front of thighs after operation, and the symptoms disappeared or relieved after 6 to 8 weeks. No complications such as abdominal organs and blood vessels injury, cerebrospinal fluid leakage, mislocation of intervertebral space, paralytic intestinal obstruction and permanent injury of genitofemoral nerve occurred. All patients were followed up for 24 months. The results showed that at the last follow-up, the Visual Analogue Scale (VAS) scores of low back pain and lower limb pain were significantly lower, and the lumbar spine scores of Japanese Orthopaedic Association (JOA) were significantly higher than before operation (P ＜ 0. 05). Conclusion Extralateral approach interbody fusion can achieve satisfactory results in the treatment of lumbar degenerative diseases, with fewer complications and higher fusion rate.

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis

Objective To analyze the effect of extralateral approach interbody fusion in the treatment of degenerative lumbar diseases. Methods A total of 50 patients with lumbar degenerative diseases admitted to our hospital were selected, and were treated with extralateral approach interbody fusion, and the therapeutic effect was observed and analyzed. Results All patients successfully completed the operation. The average amount of bleeding during operation was (145. 5 ± 4. 7) m L, the average operation time was (56. 3 ± 2. 2) min, and the average hospitalization time was (7. 2 ± 1. 5) days. Four patients suffered from hip flexion weakness after operation, and the symptoms recovered completely after two months. Six patients suffered from sensory numbness in front of thighs after operation, and the symptoms disappeared or relieved after 6 to 8 weeks. No complications such as abdominal organs and blood vessels injury, cerebrospinal fluid leakage, mislocation of intervertebral space, paralytic intestinal obstruction and permanent injury of genitofemoral nerve occurred. All patients were followed up for 24 months. The results showed that at the last follow-up, the Visual Analogue Scale (VAS) scores of low back pain and lower limb pain were significantly lower, and the lumbar spine scores of Japanese Orthopaedic Association (JOA) were significantly higher than before operation (P ＜ 0. 05). Conclusion Extralateral approach interbody fusion can achieve satisfactory results in the treatment of lumbar degenerative diseases, with fewer complications and higher fusion rate.

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion?weighted magnetic resonance imaging (IVIM?DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES).Methods The CT26 colorectal cancer xenograft model of BALB／c mice were established and divided into rhES group and control group, with 20 mice in each group.The mice of rhES group were intravenously injected with rhES 5 mg·kg－1·d－1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9%saline. 5 mice of rhES group and control group were randomly selected to perform IVIM?DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM?DWI were recorded, including true diffusion coefficient( D), pseudo?diffusion coefficient ( D?) and perfusion fraction ( f).Meanwhile, microvessel density ( MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42 ± 24.65) mm3 and (174.24 ± 28.27) mm3, respectively, without statistically significant difference ( P＝0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group ( all P＜0.05).There were no statistical significances of D value between the rhES group and control group before and after treatment ( all P＞0.05).The D? values of the rhES group were (10.940±2.834)×10－3mm2／s and (12.940±2.801)×10－3 mm2／s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10－3mm2／s and (7.898±1.603)×10－3mm2／s of control group (P＜0.05). Moreover, compared with control group, the D?value of rhES group was significantly lower in day 12 (6.848±1.460)×10－3mm2／s vs (9.950±2.596)×10－3 mm2／s, (P＜0.05). The f value of rhES group in day 8 was (0.226± 0.021)%, significantly higher than (0.178±0.016)% of control group (P＜0.01). The MVD of rhES group was significantly lower than that of control group (P＜0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment ( all P＜0.05).In addition, we found D?value of IVIM?DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.354, r＝0.555, r＝0.559, all P＜0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r＝－0.391, r＝0.538, r＝0.315, all P＜0.05). Conclusions IVIM?DWI MRI can effectively evaluate the vascular normalization in rhES?induced CT26 colorectal tumor.The parameters D? and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.[Subject words] Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis

Objective To explore the application value and safety of endoscopic submucosal dissection (ESD) and multi-band mucosectomy (EMBM) in the treatment of early esophageal cancer and precancerous lesion.Methods Seventy-two cases of early esophageal cancer and precancerous lesion that underwent endoscopic therapy from January 2010 to April 2016 in the Wuhan Central Hospital were registered for the study.The patients in the ESD group (60 cases) received ESD,while the patients in the EMBM group (12 cases) received EMBM.Retrospective analyses were made on such indicators as surgical time and treatment results,pathological diagnosis,incidence rates of long and short-term complications,and therapeutic efficacy.Results Pathological results indicated that there were 28 cases of low-grade intraepithelial neoplasm (LGIN) precancerous lesion,16 cases of high-grade intraepithelial neoplasm (HGIN) precancerous lesion and 16 cases of early esophageal cancer (EEC).The lengths of the foci were 2-6 cm,with an average length of (3.2 ±0.6)cm and the average surgical time was(82.1 ±7.5)min.Pathological detection showed that in the EMBM group there were 3 cases of LGIN,4 cases of HGIN and 5 cases of EEC.The lengths of the foci were 3-10 cm,with an average length of(4.8 ± 0.8) cm and the average surgical time was (35.0 ± 5.1) min.The rate of retrosternal pain after surgery was 41.7％ (30/72),the rate of hemorrhage was 1.4％ (1/72),and the rates of perforation,esophageal stricture,abdominal pain and fever were respectively 1.4％ (1/72),5.6％ (4/72),11.1％ (8/72) and 11.1％ (8/72).Pathological detection indicated that in the ESD group complete resection in the cases of LGIN was 96.4％ (27/28),complete resection in the cases of HGIN was 93.8％ (15/16) and complete resection in the cases of EEC was 100％ (16/16).Pathological detection after surgery indicated that the incision edges of the foci were all negative.In the ESD group,there were no cases with lesions penetrating into the muscular layer of mucosa and further into the submucous layer,while there were 2 cases in the EMBM group with lesions penetrating into the submucous layer.Examination by gastroscopy in 62 cases 2 months after surgery revealed that the healing rate of the wound surface was 100％ (62/62),and there was only 1 case that had residual incomplete healing.Fifty-eight cases had gastroscopy 6 months after surgery,and detection results indicated that there was only 1 case that had local recurrence,and 56 cases had gastroscopy 12 months after surgery,and detection results revealed that there was no case of local recurrence.16.7％ of the patients(2/72)that had residual foci or local recurrence were all the patients from the EMBM group.Conclusions ESD and EMBM were safe and effective therapeutic methods for the treatment of early esophageal cancer and precancerous lesion.ESD could completely remove foci with just one incision,with the advantages of easy pathological detection,low rates of recurrence and complication,and low injury,while EMBM on the other hand was a more prompt,safe and effective method for the treatment of lesion with broad foci,however it could not provide complete pathologic data.