Periodontitis is a chronic inflammatory disease primarily triggered by dysregulation of microbial communities and altered host immune response.It is clinically presented by alveolar bone resorption,which is one of the main causes of loosening of teeth and tooth loss.Cathepsin K(CTSK)is a highly expressed collagenase produced by osteo-clasts and can directly degrade matrix collagen proteins and indirectly increase osteoclast activity.The expression level of CTSK fluctuates in response to the progression of periodontal inflammation.The expression of Toll-like receptors is upregu-lated in periodontitis lesions.Pathogen-associated molecular pattern binds to relevant TLRs,initiating downstream im-mune pathways that promote receptor activator of nuclear factor-κB ligand-dependent osteoclastogenesis,along with in-creased expression of CTSK.Intervening in the process of alveolar bone resorption can be achieved through the regulation of CTSK.This paper provides a summary of the pathogenic mechanism of CTSK in periodontitis and highlights the research progress regarding the use of CTSK as a therapeutic target.The aim is to offer insights and references for the treatment of periodontitis.

Periodontitis is a chronic inflammatory disease primarily triggered by dysregulation of microbial communities and altered host immune response.It is clinically presented by alveolar bone resorption,which is one of the main causes of loosening of teeth and tooth loss.Cathepsin K(CTSK)is a highly expressed collagenase produced by osteo-clasts and can directly degrade matrix collagen proteins and indirectly increase osteoclast activity.The expression level of CTSK fluctuates in response to the progression of periodontal inflammation.The expression of Toll-like receptors is upregu-lated in periodontitis lesions.Pathogen-associated molecular pattern binds to relevant TLRs,initiating downstream im-mune pathways that promote receptor activator of nuclear factor-κB ligand-dependent osteoclastogenesis,along with in-creased expression of CTSK.Intervening in the process of alveolar bone resorption can be achieved through the regulation of CTSK.This paper provides a summary of the pathogenic mechanism of CTSK in periodontitis and highlights the research progress regarding the use of CTSK as a therapeutic target.The aim is to offer insights and references for the treatment of periodontitis.

ObjectiveTo clarify the scientific validity of in vivo pharmacokinetic determination of the whole drug composition in Shenbai nanosuspension in rats， and to provide methodological guidance and theoretical basis for the in vivo study of multi-component complex system of traditional Chinese medicine（TCM） preparations. MethodThe concentration of the overall components， mainly total saponins and total polysaccharides in Shenbai decoction and Shenbai nanosuspension， was determined in rat plasma at different times by area under the absorbance-wavelength curve method（AUAWC）， and the concentration of individual ginsenoside Rg₁ was determined by high performance liquid chromatography（HPLC）， and the methodology was verified. The pharmacokinetic parameters of the whole component were compared with those of ginsenoside Rg₁ to evaluate the in vivo operational characteristics of the two preparations. ResultThe methodological investigations of AUAWC and HPLC were in accordance with the requirements. AUAWC analysis showed that the overall components in both the decoction group and the nanosuspension group showed a one-compartment model， with half-life（t_1/2） of 2.43 h and 2.04 h， respectively. The relative bioavailability of Shenbai nanosuspension was 138.99%. HPLC assay showed that ginsenoside Rg₁ in the decoction group and the nanosuspension group showed a two-compartment model， with distribution half-life（t_1/2α） of 0.13 h and 2.55 h， and elimination half-life（t_1/2β） were 14.28 h and 3.85 h， respectively. The relative bioavailability of Shenbai nanosuspension was 127.49%. Compared with Shenbai decoction， the time to peak（t_max）， peak concentration（C_max） and area under the drug-time curve（AUC） of the overall components and ginsenoside Rg₁ in Shenbai nanosuspension were increased. ConclusionThe established AUAWC can be used for the pharmacokinetic study of the overall components of TCM preparations， which is complementary to the results of individual components measured by HPLC， and can provide useful reference for the in vivo study of new dosage forms of TCM.

Objective:To effectively quantify and evaluate the quality of different deformation registration algorithms, in order to enhance the possibility of implementing deformation registration in clinical practice.Methods:The Jacobian determinant mean (JDM) is proposed based on the Jacobian determinant (JD) of displacement vector field (DVF), and the Jacobian determinant error (DJDE) is introduced by incorporating the JD of the inverse DVF. The optical flow method (OF-DIR) and fast demons method with elastic regularization (FD-DIR) were tested on nasopharyngeal and lung cancer datasets. Finally, JDM and DJDE with the Jacobian determinant negative percentage (JDNP), inverse consistency error (ICE) and normalized mean square error (NMSE) were used to evaluate the registration algorithms and compare the differences evaluation indicators in different tumor images and different algorithms, and the receiver operating curve (ROC) was analyzed in evaluation.Results:In lung cancer, OF-DIR outperformed FD-DIR in terms of JDM, NMSE, DJDE and ICE, and the difference was statistically significant( z = -2.24, -4.84, t = 4.01, 6.54, P<0.05). In nasopharyngeal carcinoma, DJDE, ICE and NMSE of OF-DIR were superior to FD-DIR, and the difference was statistically significant ( t = 4.46, -7.49, z = -2.22, P<0.05), but there was no significant difference in JDM ( P>0.05). In lung cancer and nasopharyngeal carcinoma, JDNP of OF-DIR was worse than that of FD-DIR, and the difference was statistically significant ( z = -4.29, -4.02, P<0.01). In addition, DJDE is more specific and sensitive on ROC curve (AUC=0.77), and has different performance result for tumor images at different sites. Conclusions:The JDM and DJDE evaluation metrics proposed are effective for deformation registration algorithms. OF-DIR is suitable for both lung cancer and nasopharyngeal carcinoma, while the influence of organ motion on the registration effect should be considered when using FD-DIR.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective:This study aimed to explore the potential chain mediating role of psychological resilience and perceived social support in the relationship between childhood trauma and suicide risk in patients with bipolar disorder (BD). This study aimed to provide new insights for the intervention and prevention of suicide in BD patients focusing on psychosocial, familial, and social support.Methods:From March 2023 to September 2023, a total of 116 patients who were hospitalized and met the ICD-10 diagnostic criteria for BD at the Fuzhou Neuropsychiatric Hospital of Fujian province were assessed using Suicide Risk Assessment Scale, Childhood Trauma Questionnaire, Perceived Social Support Scale, and Psychological Resilience Scale. SPSS 26.0 was used for statistical analysis.Patients were divided into high and low suicide risk groups based on their scores from the Suicide Risk Assessment Scale. Statistical analysis was performed using SPSS 26.0, employing χ2 tests, t-tests, or Mann-Whitney U tests to compare demographic characteristics, clinical features, and scale scores between the two groups. A mediation model was constructed using Hayes′ Process extension for SPSS to analyze the mediating effects of psychological resilience and perceived social support on the relationship between childhood trauma and suicide risk. Results:(1)Compared with the low suicide risk group, BD patients with high suicide risk had a higher proportion of unmarried status (χ2=6.42, P=0.039), a higher proportion of depressed individuals (χ2=24.69, P<0.001), and a earlier onset age ( Z=-2.06, P=0.036). (2)Compared with the low suicide risk group, BD patients with high suicide risk had higher scores for childhood trauma, different trauma type (emotional neglect, physical neglect, emotional abuse, and physical abuse), but lower scores for perceived social support (family support, friend support, other support), and psychological resilience (toughness, strength, optimism) (all P<0.05).(3) Suicide risk scores of BD patients were significantly correlated with the scores of childhood trauma, perceived social support, and psychological resilience ( r=0.49, -0.44, -0.52, P<0.05), the scores of childhood trauma were significantly correlated with the scores of perceived social support and psychological resilience ( r=-0.57, -0.52, P<0.05). A significant correlation was found between perceived social support and psychological resilience scores ( r=0.70, P<0.05). (4)Psychological resilience and perceived social support played a chain-mediating role in the relationship between childhood trauma and suicide risk in BD patients, with a mediating effect size of 38.94%, and the confidence interval of this mediating effect did not include zero. Conclusions:Psychological resilience and perceived social support act as chain mediators in the relationship between childhood trauma and suicide risk in BD patients. The assessment and intervention targeting factors such as childhood trauma, psychological resilience, perceived social support could be incorporated into the management of suicide risk in BD patients.

Objective:This study aimed to explore the potential chain mediating role of psychological resilience and perceived social support in the relationship between childhood trauma and suicide risk in patients with bipolar disorder (BD). This study aimed to provide new insights for the intervention and prevention of suicide in BD patients focusing on psychosocial, familial, and social support.Methods:From March 2023 to September 2023, a total of 116 patients who were hospitalized and met the ICD-10 diagnostic criteria for BD at the Fuzhou Neuropsychiatric Hospital of Fujian province were assessed using Suicide Risk Assessment Scale, Childhood Trauma Questionnaire, Perceived Social Support Scale, and Psychological Resilience Scale. SPSS 26.0 was used for statistical analysis.Patients were divided into high and low suicide risk groups based on their scores from the Suicide Risk Assessment Scale. Statistical analysis was performed using SPSS 26.0, employing χ2 tests, t-tests, or Mann-Whitney U tests to compare demographic characteristics, clinical features, and scale scores between the two groups. A mediation model was constructed using Hayes′ Process extension for SPSS to analyze the mediating effects of psychological resilience and perceived social support on the relationship between childhood trauma and suicide risk. Results:(1)Compared with the low suicide risk group, BD patients with high suicide risk had a higher proportion of unmarried status (χ2=6.42, P=0.039), a higher proportion of depressed individuals (χ2=24.69, P<0.001), and a earlier onset age ( Z=-2.06, P=0.036). (2)Compared with the low suicide risk group, BD patients with high suicide risk had higher scores for childhood trauma, different trauma type (emotional neglect, physical neglect, emotional abuse, and physical abuse), but lower scores for perceived social support (family support, friend support, other support), and psychological resilience (toughness, strength, optimism) (all P<0.05).(3) Suicide risk scores of BD patients were significantly correlated with the scores of childhood trauma, perceived social support, and psychological resilience ( r=0.49, -0.44, -0.52, P<0.05), the scores of childhood trauma were significantly correlated with the scores of perceived social support and psychological resilience ( r=-0.57, -0.52, P<0.05). A significant correlation was found between perceived social support and psychological resilience scores ( r=0.70, P<0.05). (4)Psychological resilience and perceived social support played a chain-mediating role in the relationship between childhood trauma and suicide risk in BD patients, with a mediating effect size of 38.94%, and the confidence interval of this mediating effect did not include zero. Conclusions:Psychological resilience and perceived social support act as chain mediators in the relationship between childhood trauma and suicide risk in BD patients. The assessment and intervention targeting factors such as childhood trauma, psychological resilience, perceived social support could be incorporated into the management of suicide risk in BD patients.