AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

The crosstalk between macrophages and bone marrow mesen chymal stem cells （BMSCs） plays a vital role in regulating tendon-bone healing. Based on the traditional Chinese medicine （TCM） theory that the kidney governs the bones and generates marrow， yin-nourishing and kidney-tonifying Chinese medicines can promote the osteogenic differentiation of BMSCs and the M1-to-M2 polarization of macrophages， thereby facilitating tendon-bone healing. A variety of related medicinal monomers （such as diosgenin and oleanolic acid）， extracts and effective fractions （such as artificial tiger bone powder and total flavonoids of Drynaria fortunei ）， as well as compound prescriptions （such as Liuwei dihuang pill， Xujin jiegu decoction and Duhuo jisheng decoction）， can modulate the crosstalk between macrophages and BMSCs by regulating the Wnt/β-catenin， nuclear factor kappa-B， phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin and transforming growth factor-β/Smad signaling pathways. They further exert anti-inflammatory， antioxidant and osteogenic effects to effectively accelerate tendon-bone healing. However， current evidence was limited to animal experiments exhibiting such as limitations insufficent alignment between animal models and clinical injury types， research focusing mostly on single signaling pathways， and unclear core active ingredients. Future studies shall optimize animal models and carry out large-sample randomized controlled trials， clarify the interactive networks of multiple signaling pathways， and isolate the core active substances of yin-nourishing and kidney-tonifying Chinese medicines， so as to advance the precise application of traditional Chinese medicines.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

High-altitude retinopathy(HAR)is a retinal vascular disorder induced by exposure to high-altitude environments. With the increasing popularity of high-altitude travel, mountaineering, and special occupational activities, worldwide, the incidence of HAR has risen, particularly among individuals with rapid or short-term exposure to elevated altitudes. Most cases of HAR are self-limiting and gradually resolve with descent to lower altitudes. However, severe cases may result in permanent visual function impairment if not recognized and managed promptly. This review systematically summarizes the epidemiology, diagnostic progress, pathogenesis, and prevention and treatment strategies of HAR, with particular emphasis on hypoxia-associated molecular pathways involved in retinal damage, and evaluates current evidence for clinical interventions. Deepened understanding of its pathological mechanisms and clinical management strategies facilitates early identification, targeted intervention, and ocular health protection for populations exposed to high altitudes.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Objective:To investigate the incidence of visual fatigue among military pilots during flights or simulated flights and analyze the correlations among the multidimensional evaluation indicators of visual fatigue.Methods:A total of 172 pilots from an Air Force unit were selected between March 2022 and August 2023. A self-made pilot visual fatigue scale [involving the basic information, visual fatigue status scale (VFSS), and visual quality scale (VQS) was used. The visual fatigue among pilots of different types was compared. Pearson correlation analysis was used to explore the correlations between the cumulative duration of visual display terminal (VDT) and the dimensions of the VFSS, as well as between dimensions of the VFSS and the VQS. Multiple linear regression was used to identify the determinants of the score of the VQS.Results:A total of 172 questionnaires were issued, 146 of which were valid, with an effective rate of 84.88%. Among the 146 military pilots, 73 were fighter pilots and 73 were pilots of other aircraft types (20 bombers, 5 helicopters, 36 transporters, 8 trainers, and 4 fighter-bombers). There were significant differences in the scores of various dimensions and the total score of the VFSS between pilots who were different in age, aircraft types, maximum single-sortie flight durations, and in the proportion of time spent viewing cockpit displays during flight missions ( F=4.93-14.41, t=2.37-4.86, all P<0.01 or <0.05). Significant differences in visual disturbance, systemic symptoms, environmental factors, and the total visual fatigue score were observed between pilots whose total flying hours were different ( F=14.18, 4.90, 4.66, 8.12, P<0.001, =0.009,0.011, <0.001). However, there were no significant differences in the scores of any dimension or in the total score of the VFSS between pilots with a history of ocular trauma or disease and those without (all P>0.05). The cumulative duration of VDT use was positively correlated with the scores of all dimensions and the total score of the VFSS ( r=0.353, 0.303, 0.312, 0.250, 0.356, P<0.001, <0.001, <0.001, =0.002, <0.001), the dimensions of which were positively correlated with those of the VQS ( r=0.448-0.781, all P<0.01). Age ( B=1.524, 95% CI: 0.503-2.545), proportions of time spent viewing cockpit displays during flight missions ( B=3.721, 95% CI: 1.683-5.759), starburst ( B=2.346, 95% CI: 0.516-4.176), blurred vision ( B=3.517, 95% CI: 1.168-5.866), visual fluctuation ( B=2.997, 95% CI: 1.036-4.957) and halo ( B=2.415, 95% CI: 0.469-4.362) were contributors to the total visual fatigue score. Conclusions:The scores of various dimensions and the total score of visual fatigue status in military pilots can increase with age, peak in the group ages 40 to 49, and then decline. Fighter pilots experience lower levels of visual fatigue than those of other aircraft types. The visual quality scale can serve as a reference for assessing pilots′ visual fatigue status. Cumulative durations of VDT use are positively correlated with the degree of visual fatigue. Age, proportions of time spent viewing cockpit displays during flight missions, starburst, blurred vision, visual fluctuation and halo can be used to quickly assess the risk level of visual fatigue among pilots.

Objective To explore the cause of dislocation after femoral head replacement(FHR)surgery in elderly patients with failed intramedullary treatment of femoral intertrochanteric fracture(FIF).Methods Elderly patients(175 cases)with FIF who underwent FHR treatment due to failure of intramedullary nails after proximal femoral nail anti-rotation(PFNA)treatment in our hospital from December 2018 to January 2023 were selected as the research subjects.According to whether the femoral head was dislocated after FHR surgery,the patients were divided into dislocation group(45 cases)and non-dislocation group(130 cases).The clinical efficacy of FHR surgery was evaluated,and clinical data of patients(including age,gender,perioperative da-ta,etc.)was collected for comparative analysis.Multicollinearity of these factors was determined.LASSO regression analysis was used to screen for predictive factors.Based on multivariate logistic regression analysis of risk factors,simple risk scoring model was constructed using the odds ratio(OR)values of each risk factor.Receiver operating characteristic(ROC)curves were constructed to evaluate the discriminability of the model.Hosmer Lemeshow(H-L)test was used to judge the calibration of the model.Results Compared with preoperative,the Harris scores of patients at 1 and 12 months after surgery were significantly improved(P＜0.05).Postoperative complications in FHR patients were relatively low,mainly including pulmonary infection(2.86％),lower limb thrombosis(2.86％),and cardiac dysfunction(2.86％).The LASSO regression model obtained 6 predic-tive factors,among which age,neurological and muscular system diseases,surgical approach,postoperative lifestyle habits,and postoperative care were all independent influencing factors for the occurrence of femoral head dislocation(P＜0.05).The score of the simplified risk scoring model was 0～21.6 points,which can be divided into three risk levels:low risk(＜11 points),medi-um risk(11-15 points),and high risk(＞15 points).There was no significant difference in the incidence of dislocation between the two episodes of patients(P＞0.05).The model validation results showed good discrimination and calibration.Conclusion FHR can effectively improve hip joint function in elderly patients after failure of FIF intramedullary nail fixation,and there are fewer postoperative complications.Age,neurological and muscular system diseases,surgical approach,postoperative lifestyle habits,and postoperative care are independent influencing factors for the occurrence of femoral head dislocation,and should be taken seriously and prevented in clinical treatment.

Objective:To explore the value of non-invasive habitat imaging (HI) multi-parametric MRI (mpMRI) in predicting the risk of prostate cancer (PCa).Methods:In this cross-sectional study, 220 patients with PCa confirmed by radical prostatectomy (RP) who underwent multi-parametric MRI (mpMRI) scanning at Xijing Hospital, Air Force Military Medical University from January 2018 to May 2024 were retrospectively collected. Patients were divided into a training set (154 cases) and a test set (66 cases) by simple random sampling in a 7∶3 ratio. Based on mpMRI imaging, the apparent diffusion coefficient (ADC), perfusion fraction (f), and mean kurtosis (MK) of each voxel were integrated. The K-means clustering algorithm was used to divide the PCa target lesions into habitat subregions, generate habitat maps, and calculate the proportion of each habitat subregion in the entire lesion. According to the 2019 International Society of Urological Pathology (ISUP) guidelines, patients were categorized into a low-risk group (ISUP≤2, 65 cases) and a high-risk group (ISUP≥3, 155 cases). The RP specimens were matched with the habitat map to identify corresponding habitat subregions, and the ISUP grade of each subregion was individually evaluated to calculate the detection rate of high-risk PCa patients. The logistic regression analysis was applied to identify the independent risk factors associated with PCa risk, and the HI-clinical imaging model and clinical imaging model were constructed. The efficacy of the models was assessed using receiver operating characteristic curve.Results:Based on the optimal cluster number, the habitat was divided into three subregions. Habitat 1 had lower ADC and f values and higher MK values, while habitat 2 had the opposite characteristics, and habitat 3 was intermediate. The proportion of habitat 1 in the high-risk group was 28.8%, in the low-risk group was 8.9%. In the training set, the comparison of habitat subregions with pathological results showed that the detection rate of high-risk lesions was 66.9% (103/154) in habitat 1, 25.3% (39/154) in habitat 2, and 47.4% (73/154) in habitat 3. The logistic regression analysis indicated that the proportion of habitat 1 ( OR=3.03, 95% CI 1.77-5.18, P<0.001), prostate-specific antigen ( OR=1.66, 95% CI 1.04-2.66, P=0.034), and the prostate imaging reporting and data system score ( OR=1.65, 95% CI 1.00-2.70, P=0.048) as independent risk factors for high-risk PCa. In the training set, the area under the curve (AUC) for predicting PCa risk was 0.854 (95% CI 0.789-0.920) for the HI-clinical imaging model and 0.779 (95% CI 0.701-0.856) for the clinical imaging model. In the test set, the AUC values were 0.809 (95% CI 0.693-0.895) and 0.738 (95% CI 0.619-0.856), respectively. Conclusion:HI based on mpMRI can effectively predict the risk of PCa.