Objective To explore the mechanism of NLRP3 gene knockout in relation to the abnormal mucosal barrier and inflammatory factors in ulcerative colitis(UC)mice.Methods Thirty-two NLRP3-knockout(NLRP3-/-)mice and 30 C57BL/6 wild-type(WT)mice were divided randomly into six groups:NLRP3-/-blank,NLRP3-/-model,NLRP3-/-mesalazine,WT blank,WT model,and WT mesalazine groups.Except for mice in the two blank groups,mice in the other groups were given 3％dextran sodium sulfate to drink freely for 5 days to establish an UC mouse model.After successful establishment of the model,mice in each group underwent intragastric administration of the respective solution for 7 consecutive days.The general condition,body weight,disease activity index(DAI)score,and colon length were observed and evaluated in each group.Histopathological changes in the colon were observed by hematoxylin and eosin staining.ZO-1,claudin-1,occludin,tumor necrosis factor(TNF)-αand interleukin(IL)-6 expression in colon tissue were detected by immunohistochemistry.Results(1)The DAI score was significantly higher in the NLRP3-/-model group compared with the WT model group on day 12,while colon length was significantly shorter and pathological injury of the intestinal mucosa was more serious.Expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower whereas expression levels of TNF-α and IL-6 were significantly higher in the NLRP3-/-model group compared with the WT model group.(2)Regarding the two mesalazine groups,the DAI score was significantly higher and expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower in the NLRP3-/-mesalazine compared with the WT mesalazine group on day 12.Conclusions Specific knockout of the NLRP3 gene makes mice more sensitive to UC.Compared with WT mice,NLRP3-/-UC mice have more severe mucosal barrier injury and release more inflammatory factors.Mesalazine could repair the mucosal barrier and reduce inflammation in NLRP3-/-and WT UC mice.Under the same experimental conditions,mesalazine repaired the mucosal barrier more effectively in WT compared with NLRP3-/-UC mice.

Temporomandibular joint osteoarthritis(TMJOA)is a chronic degenerative disorder.Although current clinical interven-tions can effectively mitigate disease progression,they remain limited in fully reversing formed pathological structural alterations.Mesenchymal stem cell-derived exosomes(MSC-Exos),which mimic the primary therapeutic functions of mesenchymal stem cells,exhibit advantages such as excellent biocompatibility,low immunogenicity,and absence of cytotoxicity.In TMJOA,MSC-Exos exert therapeutic effects by modulating chondrocytes,immune cells,and the cartilage matrix.However,the clinical application of MSC-Exos still faces certain limitations.Enhancing their therapeutic efficacy has become a central research focus in this field.This review summarizes existing therapeutic strategies for TMJOA and explores the potential applications of MSC-Exos in TMJOA management,aiming to provide insights for future research.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective To explore the mechanism of NLRP3 gene knockout in relation to the abnormal mucosal barrier and inflammatory factors in ulcerative colitis(UC)mice.Methods Thirty-two NLRP3-knockout(NLRP3-/-)mice and 30 C57BL/6 wild-type(WT)mice were divided randomly into six groups:NLRP3-/-blank,NLRP3-/-model,NLRP3-/-mesalazine,WT blank,WT model,and WT mesalazine groups.Except for mice in the two blank groups,mice in the other groups were given 3％dextran sodium sulfate to drink freely for 5 days to establish an UC mouse model.After successful establishment of the model,mice in each group underwent intragastric administration of the respective solution for 7 consecutive days.The general condition,body weight,disease activity index(DAI)score,and colon length were observed and evaluated in each group.Histopathological changes in the colon were observed by hematoxylin and eosin staining.ZO-1,claudin-1,occludin,tumor necrosis factor(TNF)-αand interleukin(IL)-6 expression in colon tissue were detected by immunohistochemistry.Results(1)The DAI score was significantly higher in the NLRP3-/-model group compared with the WT model group on day 12,while colon length was significantly shorter and pathological injury of the intestinal mucosa was more serious.Expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower whereas expression levels of TNF-α and IL-6 were significantly higher in the NLRP3-/-model group compared with the WT model group.(2)Regarding the two mesalazine groups,the DAI score was significantly higher and expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower in the NLRP3-/-mesalazine compared with the WT mesalazine group on day 12.Conclusions Specific knockout of the NLRP3 gene makes mice more sensitive to UC.Compared with WT mice,NLRP3-/-UC mice have more severe mucosal barrier injury and release more inflammatory factors.Mesalazine could repair the mucosal barrier and reduce inflammation in NLRP3-/-and WT UC mice.Under the same experimental conditions,mesalazine repaired the mucosal barrier more effectively in WT compared with NLRP3-/-UC mice.

Objective To explore the effectiveness of a hospital-to-home transitional health management program for caregivers of children with severe encephalitis,aiming to provide a reference for optimizing transitional care models for these patients.Methods A convenience sampling method was used to select 84 children with severe encephalitis and their caregivers admitted to the neurology department of a tertiary hospital in Zhengzhou between March 2023 and June 2024.According to the admission time,they were divided into an experimental group and a control group,with 42 cases in each group.The experimental group received a hospital-to-home transitional health management program in addition to routine care,while the control group received standard care and discharge instructions.Differences in caregivers' perceived benefits,caregiver burden,disease management ability,and post-intervention outcomes of the children were compared between the 2 groups before and after the intervention.Results All 42 participants in both groups completed the study.After the intervention,the experimental group reported higher perceived benefits of(91.29±9.76)compared to(84.81±12.86)in the control group,lower caregiver burden of(48.55±7.15)compared to(54.71±11.23)in the control group,greater disease management ability of(41.83±4.97)than(37.79±5.23)in the control group,and lower difficulty in disease management of(31.52±7.82)compared to(34.55±3.96)in the control group,with all differences being statistically significant(P＜0.05).No statistically significant difference was found in the prognosis of the children between the 2 groups(P=0.500).Conclusion The hospital-to-home transitional health management program can effectively enhance caregivers'perceived benefits and disease management capabilities,reduce their caregiving burden,and provide scientific evidence for optimizing transitional care for children with severe encephalitis.

Objective:To compare the diagnostic efficacy of the added 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT imaging (tomography imaging) after early or delayed planar imaging in different types of hyperparathyroidism, and to seek for the optimal timing of preoperative imaging. Methods:A total of 339 patients (148 males, 191 females, age (52±13) years) with primary or secondary hyperparathyroidism and pathological results from January 2016 to June 2024 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. The patients were divided into primary early tomography imaging group ( n=63) and delayed tomography imaging group ( n=47), secondary early tomography imaging group ( n=89) and delayed tomography imaging group ( n=140). χ2 test was used to compare the diagnostic efficacies of early and delayed tomography imaging. Results:The difference of accuracy between primary delayed (98.40%(185/188)) and early tomography imaging (94.84%(239/252)) was statistically significant ( χ2=3.90, P=0.048). There were significant differences in sensitivity (77.29%(405/524) and 85.40%(275/322)), accuracy (75.89%(425/560) and 83.99%(299/356)) and negative predictive value (14.39%(20/139) and 33.80%(24/71)) between secondary delayed and early tomography imaging ( χ2 values: 8.33, 8.61, 10.70, all P<0.01). Conclusion:The optimal timing of preoperative 99Tc m-MIBI SPECT/CT imaging for primary and secondary hyperparathyroidism is after delayed planar imaging and after early planar imaging respectively.

Objective:To investigate the attention level of oral medicine residents in standardized training (referred to as residency training) to oral aesthetic information and its influencing factors.Methods:This study was a cross-sectional study, which included 262 residents undergoing standardized training at Hospital of Stomatology, Wuhan University in January 2020. Among them, there were 73 males and 189 females, with an age range of 23-33 (26±2) years. A questionnaire survey method was used, and the questionnaire included the basic characteristics of the subjects (gender, grade, major, identity, and having training experience in prosthodontic base or not) as well as their attention to oral aesthetic information (facial proportions, facial midline, smile line, facial contour, E-line, nasolabial angle, tooth shape and contour, and tooth proportions). Differences in the attention to oral aesthetic information among residents with different basic characteristics were compared, and a multivariable logistic regression was used to identify the influencing factors.Results:Among the 262 oral medicine residents, 256 (97.7%) believed that it was necessary to pay attention to oral aesthetic information. The differences in attention to facial proportions between residents of different genders and between those with and without training experience in the prosthodontic base were statistically significant (both P<0.05). The results of the multivariate logistic regression showed that male residents were less likely to pay attention to facial proportions compared with female residents ( OR=0.45, 95% CI: 0.23-0.88). Compared with residents specializing in orthodontics, non-orthodontic residents were less likely to pay attention to the E-line ( OR=0.14-0.27, 95% CI: 0.04-0.68) and nasolabial angle ( OR=0.14-0.31, 95% CI: 0.04-0.81). Residents who were graduate students with integrated four certificates were more likely to pay attention to the E-line compared with industry-based personnel ( OR=1.88, 95% CI: 1.01-3.49). Residents without training experience in the prosthodontic base were less likely to pay attention to the facial proportion ( OR=0.44, 95% CI: 0.20-0.97) and tooth shape and contour ( OR=0.33, 95% CI: 0.11-0.98) compared with those with such training experience in prosthodontic base. Conclusions:Oral medicine residents have a high level of attention to oral aesthetic information. Gender, major, identity, and having training experience in the prosthodontic base or not are factors that influence their attention to oral aesthetic information.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

Objective:To compare the diagnostic efficacy of the added 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT imaging (tomography imaging) after early or delayed planar imaging in different types of hyperparathyroidism, and to seek for the optimal timing of preoperative imaging. Methods:A total of 339 patients (148 males, 191 females, age (52±13) years) with primary or secondary hyperparathyroidism and pathological results from January 2016 to June 2024 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. The patients were divided into primary early tomography imaging group ( n=63) and delayed tomography imaging group ( n=47), secondary early tomography imaging group ( n=89) and delayed tomography imaging group ( n=140). χ2 test was used to compare the diagnostic efficacies of early and delayed tomography imaging. Results:The difference of accuracy between primary delayed (98.40%(185/188)) and early tomography imaging (94.84%(239/252)) was statistically significant ( χ2=3.90, P=0.048). There were significant differences in sensitivity (77.29%(405/524) and 85.40%(275/322)), accuracy (75.89%(425/560) and 83.99%(299/356)) and negative predictive value (14.39%(20/139) and 33.80%(24/71)) between secondary delayed and early tomography imaging ( χ2 values: 8.33, 8.61, 10.70, all P<0.01). Conclusion:The optimal timing of preoperative 99Tc m-MIBI SPECT/CT imaging for primary and secondary hyperparathyroidism is after delayed planar imaging and after early planar imaging respectively.