Objective:To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS).Methods:A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children′s Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results:The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses ( t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions:Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Objective:To summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.

With an aging population, the incidence of osteoporotic vertebral fractures (OVFs) is on the rise, posing new challenges for developing personalized treatment strategies. For patients who do not respond to conservative treatment, percutaneous vertebroplasty or percutaneous kyphoplasty (PVP/PKP) remains the preferred surgical option due to its minimal invasiveness and rapid recovery time. However, progressive local kyphosis (PLK) is one of the most severe complications following PVP/PKP, with an incidence rate of 1.5%-25.8%. PLK often presents with recurring thoracic and lower back pain, and in severe cases, spinal stenosis, causing symptoms like numbness and pain in the lower limbs. The severity of PLK varies, and treatments can range from conservative management and bone cement reinforcement to internal fixation or osteotomy. Current studies suggest that re-fracture of the affected vertebra, intervertebral disc degeneration, and osteonecrosis may be underlying mechanisms. These conditions shift the axial load forward, promoting postoperative PLK, which tends to progress over time. Postoperative PLK is closely associated with patient characteristics, fracture details, surgical factors, and post-surgery osteoporosis management. 1) The severity of osteoporosis, as indicated by the T-score from bone mineral density testing, can help predict postoperative PLK. While factors like age and gender influence osteoporosis severity, no direct relationship has been established between these factors and PLK. 2) Thoracolumbar fractures, old nonunion fractures, endplate fractures, or severe preoperative compression changes with kyphosis can increase PLK risk. Surgical factors, including the use of balloons or implants and the distribution of bone cement, also play a role. Personalized treatment plans should be developed based on the patient's general condition and imaging results to ensure adequate bone cement diffusion, as enhanced integration can reduce PLK risk. 3) Postoperative anti-osteoporosis therapy is also crucial; long-term therapy, particularly with teriparatide, can prevent PLK. Recognizing the related risk factors and establishing predictive models can help clinicians tailor treatments. Machine learning models, utilizing big data, are particularly adept at handling complex interrelated risk factors and may provide a powerful tool for personalized treatment in the future.

Objective To investigate the mechanism of the preventive effect of alum-borneol nanoemulsion on hypertrophic scars by observing its effect on cAMP-response element-binding protein 3-like 1(CREB3L1)and inflammatory damage in hypertrophic scar tissues of rabbit ear.Methods Thirty New Zealand big-eared white rabbits were randomly divided into blank group,model group,alum-borneol nanoemulsion low-,medium-,and high-dose groups(8.15,16.3,and 32.6 mg·mL-1),and asiaticoside group.The animal model was established by thermal injury.Topical application of appropriate drugs was given on the 14th day after successful modeling of deep Ⅱ-degree burns.Equal amounts of saline were applied externally to the blank and model groups twice daily and administered continuously until the 35th day.Histopathological changes in rabbit ear scar tissue were observed by hematoxylin-eosin(HE)staining.Masson staining was used for collagen deposition in scar tissue.Coexpression of CREB3L1/alpha-smooth muscle actin(α-SMA)in rabbit ear scar tissue was detected by immunofluorescence double-labeling assay.Enzyme-linked immunosorbent assay(ELISA)was applied for the detection of interleukin-6(IL-6)and interleukin-10(IL-10)in scar tissue.Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was applied for the detection of CREB3L1,Collagen Type I(COL-Ⅰ),Collagen Type Ⅲ(COL-Ⅲ),and α-SMA mRNA expression.Protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was detected by protein immunoblotting analysis(Western Bolt).Results Compared with the blank group,the scar proliferation index of the model group was significantly increased(P<0.01).Pathologic changes including the thickening of the dermis,the formation of dense reticular fibers,and accompaniment of inflammatory cell infiltration were observed.Masson staining reveals thickening of the dermis,disordered arrangement and large deposits of blue-stained collagen fibers.Double-labeling immunofluorescence results showed that positive expression of CREB3L1 and α-SMA in scar tissue increased.IL-6 levels were significantly increased(P<0.01),while IL-10 levels were significantly decreased(P<0.01).The relative mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA in the scar tissue of rabbit ear was significantly increased(P<0.01).The protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA was significantly increased(P<0.01).Compared with the model group,the scar proliferation index was significantly decreased after the treatment of medium-,high-dose of alum-borneol nanoemulsion and asiaticoside(P<0.01,P<0.05,P<0.01).Pathologic changes including the thinning of the dermis,as well as varying degrees of reduction of inflammatory cells and blue-stained collagen fibers were found.Double-labeling immunofluorescence showed positive expression of CREB3L1 and α-SMA in scar tissue decreased.IL-6 levels significantly reduced(P<0.01),while IL-10 levels significantly raised(P<0.01).The alum-borneol nanoemulsion medium-,high-dose and asiaticoside groups could significantly down-regulate the mRNA expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(all P<0.01),and reduce the protein expression of CREB3L1,COL-Ⅰ,COL-Ⅲ,and α-SMA(P<0.05,P<0.01).Conclusion Alum-borneol nanoemulsion may prevent hyperplastic scar formation by regulating the expression of CREB3L1 and related fibrotic proteins and reducing inflammatory level,which enriches the scientific connotation of"prevention of disease from exacerbating"and"treatment of the disease before its onset"in Chinese medicine.

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.
Humans ; Antioxidants/metabolism* ; Ferroptosis ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Iron Overload/metabolism*

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis

OBJECTIVE: To review the clinical research progress of spinal epidural lipomatosis (SEL). METHODS: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. RESULTS: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. CONCLUSION SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.
Humans ; Decompression, Surgical/methods* ; Epidural Space/surgery* ; Lipomatosis/surgery* ; Magnetic Resonance Imaging ; Spinal Cord Diseases/surgery*

Delirium is a common complication after stroke. Post-stroke delirium is associated with the poor outcome and increased mortality. This article reviews the screening tools, predictive factors and predictive models of post-stroke delirium.

Objective:To construct a predictive model of post-stroke delirium (PSD) in patients with acute ischemic stroke (AIS), and to verify its predictive value.Methods:Patients with AIS admitted to the Department of Neurology, Lianyungang Hospital Affiliated to Xuzhou Medical University from February to May 2022 were enrolled prospectively. They were divided into modeling group and validation group according to the order of enrollment. Depending on whether the patients had delirium or not, the patients in the modeling group were divided into delirium group and non-delirium group. The independent risk factors for PSD were determined by multivariable logistic regression analysis, and the prediction model of PSD was constructed accordingly. The predictive value of the model was verified by the receiver operating characteristic curve. Results:Three hundred and fifty patients with AIS were included in the modeling group, of which 71 (20.28%) had PSD. The validation group included 150 patients with AIS, and 36 of them (24.00%) had PSD. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.036, 95% confidence interval [ CI] 1.000-1.074; P=0.050], National Institutes of Health Stroke Scale (NIHSS) score ( OR 1.607, 95% CI 1.438-1.797; P<0.001), neutrophil/lymphocyte ratio (NLR) ( OR 1.135, 95% CI 1.016-1.267; P=0.025), and atrial fibrillation ( OR 5.528, 95% CI 1.315-23.245; P=0.020) were the independent risk factors for PSD. The predictive model was Z=0.036×age+0.475×NIHSS score+0.127×NLR+1.710×assignment of atrial fibrillation - 10.160. The area under the curve of the model was 0.935, and the sensitivity and specificity were 97.2% and 82.5% respectively. Conclusion:This model can effectively predict the PSD risk of patients with AIS, with higher sensitivity and specificity, and can provide a basis for PSD screening of patients with AIS.

Objective To investigate the influence of menstrucal cycle and anatomic site on the fractional anisotropy (FA) values of diffusion tensor imaging (DTI) in normal breast. Methods Prospectively enrolled 96 volunteers, who have identified with normal menstrucal phase and without breast diseases were found via the breast examination, ultrasound and MRI scan. The cases were divided into three groups according to menstrucal phase: menstrual period group(menstrual cramps 1 to 6 d), proliferative phase group(menstrual cramps 7 to 14 d) and secretory phase group(menstrual cramps 15 d to the next), and each group consisted of 32 subjects. All subjects were performed bilateral breast cross-sectional T1WI, T2WI, DWI and DTI scaning. On the nipple level figture, the mammary gland was divided into three regions including the anterior, central and posterior parts, and the FA values of the different phases and regions were measured. The Kruskal-Wallis H test was applied to analyse the difference of FA values in different menstrual phase and anatomic site. Results The FA values of the anterior region in menstrual phase, proliferative phase and secretary phase were 0.21 ± 0.07, 0.24 ± 0.09 and 0.17 ± 0.07, and the difference had significant difference(P=0.014).The FA values of the central region were respectively 0.15±0.08, 0.18±0.09 and 0.15±0.07, and without the statistically significant difference(P=0.090). The FA values of the posterior region were 0.21 ± 0.11, 0.24 ± 0.13 and 0.16 ± 0.11, and also showed significant difference(P=0.002). In different regions, the difference of FA values between menstrual phases and proliferative phases were also had statistically significant(P=0.018, 0.045, respectively). In the same region, the FA value was lowest in the secretary phase, and the proliferative phase was slightly higher than menstrual phase. Conclusion The FA values are affected by menstrual cycle and anatomic site.