Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

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*

Objective:To study the outcomes of the modified Devine + Shiraki surgical approach in the treatment of severe concealed penis.Methods:A retrospective analysis was conducted on the clinical data of initially treated patients with severe concealed penis admitted to the Department of Urology, Henan Provincial People’s Hospital from March 2020 to September 2022. The therapeutic effects of three surgical approaches (Devine, Shiraki, and modified Devine + Shiraki) were analyzed and compared. The Devine approach mainly focuses on eliminating the pathological morphology of the concealed penis, thoroughly releasing the penile shaft, and correcting the concealed state; the Shiraki approach emphasizes the rational distribution of skin flaps; the key of the modified Devine + Shiraki approach lies in combining the advantages of the two approaches, achieving both complete correction of the concealed state and rational distribution of skin flaps. Improvements were made to the conventional surgical sequence: skin flap distribution was pre-designed before correcting the concealed penis to avoid difficulties in skin flap arrangement caused by degloving, thereby preventing postoperative complications such as stricture rings, lymphedema, or erectile pain. Three months after the operation, follow-up was performed to assess incision healing, presence of lymphedema or stricture rings, satisfaction with penile exposure, recurrence of the concealed state, urination patency, presence of urethral injury, and normal erectile function. A patient satisfaction survey was conducted 6 months after the operation. Measurement data with normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison among the three groups; categorical variables were expressed as case numbers and percentages, and chi-square test was used for comparison among the three groups. Results:Eighty, fifty, and forty-five male children were enrolled in the Devine + Shiraki group, Devine group, and Shiraki group, respectively. There were no statistically significant differences in age and body mass index (BMI) among the three groups [age: (7.6±4.5) years vs. (7.2±4.4) years vs. (6.7±4.2) years, F=0.61, P=0.546; BMI: (17.4±3.1) kg/m 2 vs. (17.7±3.2) kg/m 2 vs. (18.0±3.3) kg/m 2,F=0.57, P=0.565]. During surgery, all concealed penile shafts were completely released, and the penile skin was rationally distributed. The postoperative follow-up period ranged from 3 months to 18 months, with an average follow-up time of 13.6 months. At the 3-month postoperative follow-up, all three groups showed satisfactory wound healing with no signs of infection or skin flap necrosis; penile skin coverage was adequate, and all children demonstrated unobstructed urination without evidence of urethral injury; normal erectile function was preserved in all cases, with no reports of erectile dysfunction or pain. The recurrence rate of the concealed penis in the Devine + Shiraki group was significantly lower than that in the Devine group and Shiraki group, with a statistically significant difference [0 (0/80) vs. 6.0% (3/50) vs. 31.1% (14/45), χ2=32.88, P<0.001]; the proportion of patients without postoperative lymphedema and stricture rings in the Devine + Shiraki group was higher than that in the Devine group and Shiraki group, with a statistically significant difference [97.5% (78/80) vs. 70.0% (35/50) vs. 86.7% (39/45), χ2=20.39, P<0.001]. The Devine+ Shiraki, Devine, and Shiraki groups reported postoperative satisfaction in 76 (95.0%), 35 (70.0%), and 31 (68.9%) cases, respectively. Conclusion:The modified Devine + Shiraki surgical approach has definite efficacy, good safety, and a low incidence of complications, and can be used as an option for the treatment of severe concealed penis.

Objective To test the longitudinal mediating mechanism of kinesophobia between family functioning and exercise adherence in elderly patients with postoperative adjacent vertebral re-fracture after osteoporotic vertebral compression fracture(OVCF).Methods Convenience sampling method was used to admit to the Department of Orthopaedics of a tertiary hospital in Xuzhou City with adjacent vertebral re-fracture after OVCF were conveniently selected as the survey subjects,and longitudinal investigation was conducted using the APGAR,Functional Exercise Adherence Scale,and TSK Scale.Unconditional potential growth model,structural equation and Bootstrap method were used for statistical analysis.Results A total of 232 valid questionnaires were collected.Longitudinal mediation modeling revealed that the intercept of family functioning significantly negatively predicted the intercept of kinesophobia(β=-0.456,P＜0.001)and the slope of family functioning significantly negatively predicted the slope of kinesophobia(β=-0.962,P＜0.001).The intercept for kinesophobia significantly negatively predicted the intercept for exercise adherence(β=-0.623,P＜0.001)and significantly negatively predicted the slope for exercise adherence(β=-0.354,P=0.013).Conclusion The initial level and rate of development of kinesophobia play a fully longitudinal mediating role in the development of family functioning on exercise adherence.Medical professionals should assess and manage patients'family functioning and kinesophobia in a timely manner,and rationally utilize their interrelationships to improve the level of exercise adherence as much as possible.

Objective:To analyse the clinical characteristics of 214 cases of paediatric high altitude pulmonary edema（HAPE）and the efficacy of dexamethasone in adjunctive therapy.Methods:This retrospective study analyzed 214 pediatric cases of HAPE admitted to the Department of Paediatrics of the General Hospital of Tibetan Military between June 2015 to June 2017 and June 2019 to June 2021.Patients were divided into dexamethasone-treated group and dexamethasone-untreated group.Baseline data，clinical characteristics were collected to evaluate the treatment efficacy and drug side effects.Results:There were 107 children in each of the two groups with a median age of 8（5，11）years. The median age of the dexamethasone-treated group was 9（6，12）years and the mean age of the dexamethasone-untreated group was 7（3，10）years. The proportion of male children was 69.60%（149/214）；the onset of illness was mostly concentrated within 72 hours，accounting for 97.20%（208/214）of the cases；83.18%（178/214）of the cases had symptoms of combined upper respiratory tract infection before entering the plateau. The most important clinical symptoms of the children were cough（86.92%，186/214），cyanosis（70.09%，150/214），and shortness of breath（66.36%，142/214）. The proportion of auscultatory rhonchi was 83.18%（178/214），and all cases showed positive findings on chest radiography. After the dexamethasone regimen，the overall cure rate of the children was 94.39%，the average disappearance time of the symptoms and signs was（40.52±7.85）h，and the average hospital stay was（3.60±1.90）d. After treatment with the dexamethasone-free regimen，the overall cure rate was 92.52%，the mean time to disappearance of symptoms and signs was（42.10±7.62）h，and the mean length of stay in the hospital was(3.84±2.08)d. There was no significant difference in the cure rate，the disappearance time of symptoms and signs，and the average hospitalisation days between the two groups（ P>0.05），but a total of 11 children in the dexamethasone-treated group experienced adverse drug reactions，and no children in the dexamethasone-untreated group experienced adverse drug reactions. Conclusion:Han Chinese male children，particularly those with upper respiratory infections，should be closely monitored for HAPE risk within three days of ascending to high altitudes. This study does not recommend the use of dexamethasone for pediatric HAPE due to the lack of therapeutic benefits and potential adverse effects.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.

Objective:To analyse the clinical characteristics of 214 cases of paediatric high altitude pulmonary edema（HAPE）and the efficacy of dexamethasone in adjunctive therapy.Methods:This retrospective study analyzed 214 pediatric cases of HAPE admitted to the Department of Paediatrics of the General Hospital of Tibetan Military between June 2015 to June 2017 and June 2019 to June 2021.Patients were divided into dexamethasone-treated group and dexamethasone-untreated group.Baseline data，clinical characteristics were collected to evaluate the treatment efficacy and drug side effects.Results:There were 107 children in each of the two groups with a median age of 8（5，11）years. The median age of the dexamethasone-treated group was 9（6，12）years and the mean age of the dexamethasone-untreated group was 7（3，10）years. The proportion of male children was 69.60%（149/214）；the onset of illness was mostly concentrated within 72 hours，accounting for 97.20%（208/214）of the cases；83.18%（178/214）of the cases had symptoms of combined upper respiratory tract infection before entering the plateau. The most important clinical symptoms of the children were cough（86.92%，186/214），cyanosis（70.09%，150/214），and shortness of breath（66.36%，142/214）. The proportion of auscultatory rhonchi was 83.18%（178/214），and all cases showed positive findings on chest radiography. After the dexamethasone regimen，the overall cure rate of the children was 94.39%，the average disappearance time of the symptoms and signs was（40.52±7.85）h，and the average hospital stay was（3.60±1.90）d. After treatment with the dexamethasone-free regimen，the overall cure rate was 92.52%，the mean time to disappearance of symptoms and signs was（42.10±7.62）h，and the mean length of stay in the hospital was(3.84±2.08)d. There was no significant difference in the cure rate，the disappearance time of symptoms and signs，and the average hospitalisation days between the two groups（ P>0.05），but a total of 11 children in the dexamethasone-treated group experienced adverse drug reactions，and no children in the dexamethasone-untreated group experienced adverse drug reactions. Conclusion:Han Chinese male children，particularly those with upper respiratory infections，should be closely monitored for HAPE risk within three days of ascending to high altitudes. This study does not recommend the use of dexamethasone for pediatric HAPE due to the lack of therapeutic benefits and potential adverse effects.

Objective:To study the outcomes of the modified Devine + Shiraki surgical approach in the treatment of severe concealed penis.Methods:A retrospective analysis was conducted on the clinical data of initially treated patients with severe concealed penis admitted to the Department of Urology, Henan Provincial People’s Hospital from March 2020 to September 2022. The therapeutic effects of three surgical approaches (Devine, Shiraki, and modified Devine + Shiraki) were analyzed and compared. The Devine approach mainly focuses on eliminating the pathological morphology of the concealed penis, thoroughly releasing the penile shaft, and correcting the concealed state; the Shiraki approach emphasizes the rational distribution of skin flaps; the key of the modified Devine + Shiraki approach lies in combining the advantages of the two approaches, achieving both complete correction of the concealed state and rational distribution of skin flaps. Improvements were made to the conventional surgical sequence: skin flap distribution was pre-designed before correcting the concealed penis to avoid difficulties in skin flap arrangement caused by degloving, thereby preventing postoperative complications such as stricture rings, lymphedema, or erectile pain. Three months after the operation, follow-up was performed to assess incision healing, presence of lymphedema or stricture rings, satisfaction with penile exposure, recurrence of the concealed state, urination patency, presence of urethral injury, and normal erectile function. A patient satisfaction survey was conducted 6 months after the operation. Measurement data with normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison among the three groups; categorical variables were expressed as case numbers and percentages, and chi-square test was used for comparison among the three groups. Results:Eighty, fifty, and forty-five male children were enrolled in the Devine + Shiraki group, Devine group, and Shiraki group, respectively. There were no statistically significant differences in age and body mass index (BMI) among the three groups [age: (7.6±4.5) years vs. (7.2±4.4) years vs. (6.7±4.2) years, F=0.61, P=0.546; BMI: (17.4±3.1) kg/m 2 vs. (17.7±3.2) kg/m 2 vs. (18.0±3.3) kg/m 2,F=0.57, P=0.565]. During surgery, all concealed penile shafts were completely released, and the penile skin was rationally distributed. The postoperative follow-up period ranged from 3 months to 18 months, with an average follow-up time of 13.6 months. At the 3-month postoperative follow-up, all three groups showed satisfactory wound healing with no signs of infection or skin flap necrosis; penile skin coverage was adequate, and all children demonstrated unobstructed urination without evidence of urethral injury; normal erectile function was preserved in all cases, with no reports of erectile dysfunction or pain. The recurrence rate of the concealed penis in the Devine + Shiraki group was significantly lower than that in the Devine group and Shiraki group, with a statistically significant difference [0 (0/80) vs. 6.0% (3/50) vs. 31.1% (14/45), χ2=32.88, P<0.001]; the proportion of patients without postoperative lymphedema and stricture rings in the Devine + Shiraki group was higher than that in the Devine group and Shiraki group, with a statistically significant difference [97.5% (78/80) vs. 70.0% (35/50) vs. 86.7% (39/45), χ2=20.39, P<0.001]. The Devine+ Shiraki, Devine, and Shiraki groups reported postoperative satisfaction in 76 (95.0%), 35 (70.0%), and 31 (68.9%) cases, respectively. Conclusion:The modified Devine + Shiraki surgical approach has definite efficacy, good safety, and a low incidence of complications, and can be used as an option for the treatment of severe concealed penis.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.