Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

ObjectiveAccording to the etiology， pathogenesis， and clinical characteristics of dry eye （DE）， this paper aims to analyze existing DE animal models to provide recommendations for building more clinically relevant DE models that integrate traditional Chinese and Western medicine. MethodsBy the retrieval and analysis of relevant literature on DE animal experiments， combined with expert consensus， an evaluation scale was created to assess relevance from the perspectives of pathogenesis， diagnostic criteria， and traditional Chinese medicine （TCM） differentiation. On the basis of data provided by the literature， the clinical relevance was evaluated for the animal models constructed in the literature. ResultsAmong the existing methods for establishing a DE animal model， benzalkonium chloride eye-drop induction showed the highest clinical relevance， demonstrating 98% alignment with Western medicine. However， current models generally showed higher relevance to Western medicine than to TCM， and there was a lack of models integrating disease with syndrome. ConclusionAs DE involves diverse causes and pathogenesis， single-factor models cannot fully simulate the complex pathology of DE. Future research should focus on building multi-mechanism DE models， exploring new etiological directions， standardizing model evaluation systems， and promoting integration of traditional Chinese and Western medicine. This will help precisely simulate the pathophysiological process of human DE and provide more valuable guidance for clinical diagnosis and treatment， ultimately enhancing patient outcomes and satisfaction.

Intelligent acupuncture-moxibustion medical equipment is an important force in promoting the inheritance, innovation, and modernization of acupuncture-moxibustion. This paper reviews the development status of intelligent acupuncture-moxibustion medical equipment and related new technologies, as well as the challenges faced. It is found that, with the advancement of technologies such as big data and artificial intelligence, acupuncture-moxibustion medical equipment has shown characteristics of greater precision, miniaturization, intelligence, and portability. However, deficiencies remain in areas such as standardization and regulation, including relatively low rates of effective transformation and a lack of innovation in research outcomes. Therefore, there is an urgent need to formulate corresponding strategies: improving the development of relevant standards for intelligent acupuncture-moxibustion medical equipment, encouraging the integration of medicine and engineering, cultivating interdisciplinary talents, and strengthening the protection of invention patents. It is necessary to establish a demand-oriented pathway connecting "equipment development, equipment evaluation, product formation" through multiple stages such as talent training and research project initiation, thereby promoting the modernization and standardization of intelligent acupuncture-moxibustion medical equipment and supporting the revitalization of traditional medicine.
Moxibustion/instrumentation* ; Humans ; Acupuncture Therapy/trends* ; Artificial Intelligence

OBJECTIVE: To analyze the disease burden of pelvic fractures at the global, regional, and national levels from 1990 to 2023 using data from the 2023 Global Burden of Disease Study (GBD), and to predict the disease burden through 2050. METHODS: Leveraging data from the GBD 2023, this study investigated the disease burden of pelvic fractures across 204 countries and regions. Assessment indicators included incidence rate, prevalence rate, and years lived with disability (YLDs). The Joinpoint regression model was employed to analyze trends in pelvic fracture burden from 1990 to 2023, while the average annual percentage change (AAPC) was used to quantify this temporal trend. The relationship between the socio-demographic index and pelvic fracture burden was evaluated. Furthermore, the long short-term memory (LSTM) model was applied to predict trends in pelvic fracture burden through 2050. RESULTS: In 2023, the estimated number of new pelvic fracture cases globally was 7 479 884 [95% uncertainty interval ( UI): 5 293 401-10 611 876], representing a 42.74% increase from 1990. In the same year, the number of prevalent pelvic fracture cases and YLDs were 23 007 508 (95% UI: 21 021 518-25 327 165) and 3 909 228 person-years (95% UI: 2 725 498-5 194 385), respectively. Additionally, age-standardized rates exhibited an opposing downward trend. Significant disparities in the disease burden of pelvic fractures were identified across different age groups, genders, and social contexts. According to predictions from the LSTM model, the global age-standardized incidence rate (ASIR) of pelvic fractures will be approximately 88.44 per 100 000 persons by 2050, while the total number of incident cases will rise to 8 547 095. CONCLUSION Although the overall incidence rate, prevalence rate, and YLDs of pelvic fractures have exhibited an upward trend over the past three decades, the ASIR, age-standardized prevalence rate (ASPR), and age-standardized years of life lost rate (ASYR) have shown a downward trend. It is predicted that over the upcoming 26-year period, the age-standardized rate of disease burden due to pelvic fractures will further decrease, while the number of incident cases and prevalent cases will continue to exhibit an upward trend. Formulating more targeted disease prevention strategies is critical to addressing disparities across genders, regions, and other dimensions, and to mitigating the burden of pelvic fractures.
Humans ; Fractures, Bone/epidemiology* ; Pelvic Bones/injuries* ; Male ; Female ; Middle Aged ; Adult ; Incidence ; Prevalence ; Aged ; Global Burden of Disease/trends* ; Global Health ; Adolescent ; Cost of Illness ; Young Adult ; Forecasting ; Disability-Adjusted Life Years ; Memory, Short-Term

Bone tuberculosis is one of the main lesions of extrapulmonary tuberculosis, and the affected site shows local pain and limited movement, and the severe patients face a higher risk of teratogenicity and disability. Especially in the context of the increasing spread of multidrug-resistant tuberculosis, it is particularly urgent to seek innovative treatment options. In recent years, vitamin D plays an important role in the prevention and treatment of bone tuberculosis, and the mechanism of action has been continuously explored. At the same time, vitamin D receptor gene polymorphism has also been found to be closely related to the susceptibility and risk of bone tuberculosis. This article reviewed the relationship between vitamin D and its receptor gene polymorphisms and the susceptibility to bone tuberculosis. It was found that vitamin D deficiency increased the susceptibility to bone tuberculosis in both adults and children, and multiple genotypes of vitamin D receptor had an effect on the susceptibility to bone tuberculosis, especially FokⅠ genotype. It may also be one of the reasons for the increase in the number of bone tuberculosis. Through the study of the relationship between vitamin D and its receptor gene polymorphism and the susceptibility to bone tuberculosis, some factors inducing bone tuberculosis can be avoided, and related new drugs can be more targeted, such as vitamin D supplements, gene receptor related antagonists, etc. To provide more systematic and targeted strategies for the prevention and treatment of bone tuberculosis.
Humans ; Receptors, Calcitriol/genetics* ; Genetic Predisposition to Disease ; Polymorphism, Genetic ; Vitamin D/metabolism* ; Tuberculosis, Osteoarticular/metabolism*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

OBJECTIVE: To compare clinical efficacy of tibial transverse transport(TTT) combined with antibiotic-loaded bone cement (ABC) and TTT in treating diabetic foot ulcer (DFU). METHODS: A retrospective analysis was conducted on 60 patients with DFU treated from January 2019 to January 2023. They were divided into bone cement group and bone transfer group according to different treatment methods, with 30 patients in each group. There were 20 males and 10 females in bone cement group, aged from 61 to 76 years old with an average of (68.15±4.85) years old;the course of ulcer disease ranged from 7 to 28 months with an average of (15.28±5.52) months;16 patients were grade 3 and 14 patients were grade 4 according to Wagner classification; TTT combined with ABC treatment was performed. There were 22 males and 8 females in bone transfer group, aged from 60 to 75 years old with average of (67.85±4.62) years old;the course of ulcer disease ranged from 6 to 29 months with an average of (14.35±5.21) months;17 patients were grade 3 and 13 patients were grade 4 according to Wagner classification;TTT was performed. The control time of wound infection, duration of antibiotic use, frequency of debridement, weight-bearing time of the affected limb, healing time of ulcer surface and recurrence of infection were compared between two groups. Visual analogue scale (VAS) and ankle brachial index (ABI) between two groups was compared before operation and 2 and 6 months after operation. RESULTS: Sixty patients were followed up for 12 to 24 months with average of (17.24±4.42) months. The control time of wound infection, duration of antibiotic use, frequency of debridement, weight-bearing time of the affected limb, and healing time of ulcer surface in bone cement group were (11.02±2.14) days, (12.7±3.5) days, (1.2±0.4) times, (90.02±2.75) days, and (2.32±3.45) months, respectively;while in bone transfer groups were (20.14±3.15) days, (20.4±4.5) days, (2.2±0.8) times, (106.64±8.35) days, and (4.53±3.12) months respectively; bone cement group was superior to bone transfer group, and the differences were statistically significant(P<0.05). Comparisons of VAS and ABI before and after treatment between two groups showed preoperative VAS and ABI in bone cement group were (6.71±0.73) points and (0.25±0.04) respectively, and those in bone transfer group were (6.87±0.17) points and (0.27±0.03) respectively. At 2 months after operation, VAS and ABI in bone cement group were (3.71±0.47) points and (0.61±0.03) respectively, and those in bone transfer group were (3.79±0.70) points and (0.59±0.05) respectively;postoperative VAS and ABI at 6 months in bone cement group were (2.26±0.13) points and (0.80±0.05) respectively, and those in bone transfer group were (2.57±0.17) points and (0.79±0.04) respectively;postoperative VAS and ABI between groups were improved at each time points compared with those of before operation (P<0.05). In bone cement group, there were 2 patients with ulcer recurrence and 1 patient with gangrene;while in bone transfer group, 5 patients with recurrence of infection, 2 patients with recurrence of ulcer and 1 patient with gangrene;the recurrence rate of infection in bone cement group were lower than that in bone transfer group (P<0.05). CONCLUSION The combination of TTT and ABC in treating DFU has a good therapeutic effect, which could be shorten the infection control time, ulcer healing time and antibiotic use time, effectively relieve pain, reduce the recurrence rate of infection and improve the quality of life of patients.
Humans ; Male ; Female ; Aged ; Bone Cements/therapeutic use* ; Middle Aged ; Anti-Bacterial Agents/therapeutic use* ; Diabetic Foot/therapy* ; Retrospective Studies ; Tibia/surgery*