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.

ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture （JDJM） in treating synovial lesions in knee osteoarthritis （KOA）. MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group （n=8） and a model group （n=35）. The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage， with a modeling period of 6 weeks， resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group， celecoxib group， JDJM group and JDJM+740Y-P group， each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg^-1， while the JDJM was administered a single dose of 6.8 mL·kg^-1 （4.515 2 g·kg^-1） of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway activator + JDJM group received 4.515 2 g·kg^-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg^-1 740Y-P. For a period of 6 weeks， the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period， the knee joint pain threshold and circumference were measured， and hematoxylin-eosin （HE） staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay （ELISA） measured the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-18） and tumor necrosis factor-α （TNF-α） in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， NOD-like receptor protein 3 （NLRP3）， cysteine-requiring aspartate protease-1 （Caspase-1） and gasdermin D （GSDMD） in the synovial tissues. Immunohistochemical （IHC） assay was performed to assess the protein expression of NLRP3， Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD. ResultsCompared to the blank group， the model group showed a significant increase in knee joint circumference and decrease in pain threshold， the synovial tissue pathology score was higher （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid significantly increased （P<0.01）. PI3K， Akt， mTOR phosphorylation as well as mRNA and protein expression increased （P<0.01）， while the mRNA and protein expression levels of NLRP3， Caspase-1 and GSDMD also significantly increased （P<0.01）. Compared to the model group， the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold， the synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid decreased （P<0.01）. The mRNA and protein expression of p-PI3K， p-Akt， p-mTOR， NLRP3， Caspase-1 and GSDMD were reduced （P<0.01）. Compared to the JDJM group， the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions， an increase in knee joint circumference， and a decrease in pain threshold. The synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid were higher （P<0.01）. The mRNA and protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD increased （P<0.01）. ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues， inhibiting pyroptosis， reducing inflammatory factor release， and protecting bony structures.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

Ulcerative colitis （UC） is a chronic， non-specific intestinal inflammatory disease. Its pathogenesis is complex， involving interactions among genetic， immune， and environmental factors， and remains incompletely elucidated. Mitochondrial damage can trigger the abnormal release of mitochondrial damage-associated molecular patterns （mtDAMPs）， activating inflammatory pathways and thereby exacerbating the inflammatory response in UC. Mitophagy， a core mitochondrial quality control mechanism， can clear damaged mitochondria and effectively reduce the abnormal release of mtDAMPs and the accumulation of harmful substances， thereby mitigating inflammatory damage resulting from mitochondrial dysfunction. Mitophagy plays a crucial role in maintaining the integrity of the intestinal epithelial barrier function and in the prevention and intervention of UC. Notably， the function of the spleen governing transportation and transformation in traditional Chinese medicine shares similarities with the role of mitochondria in energy transformation and substance metabolism. Furthermore， the pathological state of the spleen failing in transportation and transformation may be related to mitochondrial dysfunction， while the pathogenic characteristics of "endogenous turbid pathogen" align with the inflammatory cascade responses triggered by abnormal release of mtDAMPs. Based on this theoretical correlation， this paper aims to explore the correlation between the traditional Chinese medicine theory of "spleen dysfunction in essence distribution leading to endogenous turbid pathogens" and mitophagy. Using the correlation as an entry point， the potential role of mitophagy in the pathogenesis of UC was elucidated. Additionally， by considering the epidemiological characteristics of UC in the Southwest region of China， a new thinking for the treatment of UC from the perspective of turbid pathogens was proposed based on the "fortifying the spleen and resolving turbidity" method to provide theoretical support and research enlightenment for further exploring the prevention and treatment of UC with traditional Chinese medicine.

Introduction: Empty sella (ES) is characterized by herniation of the subarachnoid space into the sella turcica, leading to pituitary flattening. Although often considered incidental, ES is increasingly recognized as a radiological marker of idiopathic intracranial hypertension (IIH) which classically presents with headache and visual loss. Importantly, IIH may also present with otolaryngological manifestations such as pulsatile tinnitus, hearing loss, and vertigo. Audiovestibular symptoms have been reported in up to 88.9% of patients with primary ES, with sensorineural hearing loss being the most frequent, while pulsatile tinnitus occurs in approximately 58% of IIH cases. Case: A 51-year-old female presented with 3 months of progressively worsening headaches, rapid deterioration of left-sided hearing, and a 20-kg weight gain over 1 year. Audiometry confirmed moderate left sensorineural hearing loss. Examination revealed a normotensive female with a body mass index of 35 kg/m² and diplopia on left upward gaze without evidence of ophthalmoplegia. The rest of the neurological examination was unremarkable. There was no evidence of papilledema or Cushingoid features. Repeat magnetic resonance imaging brain in 2025 showed persistent partial ES and loss of the posterior pituitary bright spot without an intracranial mass lesion or venous sinus thrombosis. There was no biochemical evidence of hypopituitarism or Cushing’s syndrome. Autoimmune markers were unremarkable. Lumbar puncture demonstrated a mildly elevated opening pressure of 23 mmHg with normal CSF composition. Based on the clinical and radiological findings, early IIH was diagnosed. She was treated with acetazolamide, and prescribed tirzepatide for weight reduction, resulting in improvement in headache and tinnitus. Conclusion IIH can manifest with partial ES and audiovestibular symptoms related to raised intracranial pressure. Early recognition is important, and IIH should be suspected in patients with pulsatile tinnitus or progressive sensorineural hearing loss. Acetazolamide and weight management remain the mainstay of treatment, with emerging evidence supporting a potential role for glucagon-like peptide-1 receptor agonists in reducing intracranial pressure.
Pseudotumor Cerebri ; Tinnitus ; Hearing Loss

Objective To investigate the predictive efficacy of serum nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3),cystatin C(CysC)and Neuritin in postoperative neurological function recov-ery in patients with spinal fracture complicated with spinal cord nerve injury(SCI).Methods A total of 107 patients with spinal fracture complicated with SCI from July 2021 to July 2023 were selected and followed up for 6 months after treatment.They were divided into good recovery group(76 cases)and poor recovery group(31 cases)according to postoperative neurological function recovery.The clinical data,serum NLRP3,CysC and Neuritin levels of the two groups were compared,and the correlation of serum NLRP3,CysC,Neuritin and Frankel grades and their effects on postoperative neurological function recovery were analyzed.The predictive efficacy of serum NLRP3,CysC and Neuritin on postoperative neurological recovery was evaluated.Results There were statistically significant differences between the two groups in the proportion of time from injury to hormone drug use ≥8 h,vertebral canal encroachation rate≥50％and Frankel grade(P＜0.05).The levels of NLRP3,CysC and Neuritin in poor recovery group were higher than those in good recovery group(P＜0.05).Serum NLRP3,CysC and Neuritin levels were gradually decreased in Frankel grade A,B,C and D patients(P＜0.05).Serum NLRP3,CysC and Neuritin were negatively correlated with Frankel grades(P＜0.05).Serum NLRP3,CysC and Neuritin were independent risk factors for postoperative neurological function recovery in patients with spinal fracture complicated with SCI(P＜0.05).The area under the curve(AUC)predicted by serum NLRP3,CysC and Neuritin was 0.813,0.774 and 0.757,the sensitivity was 74.19％,77.42％and 70.97％,and the specificity was 82.89％,68.42％and 81.58％,respectively.The AUC of the combined prediction of the three indexes was 0.927,the sensitivity was 83.87％,and the specificity was 85.53％,and the prediction value was significantly higher than that predicted by each index alone(P＜0.05).Conclusion Serum NLRP3,CysC and Neuritin are independent risk factors for postoperative neurological function recovery in patients with spinal fracture complicated with SCI,and their combined predictive value is relatively reliable.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objectives:To systematically evaluate the effects of spinal osteotomy and spinal cord blood flow(SCBF)on the spinal cord,and to explore the safe range of osteotomy.Methods:The relevant research liter-atures on spinal osteotomy shortening and SCBF in CNKI,Wanfang,VIP,PubMed,Cochrane Library,EM-BASE and CBM databases published before May 2024 were searched by computer.Two researchers indepen-dently conducted literature screening and extracted data(research design,sample size,and outcome indicators).The quality of the included literatures was evaluated by using the improved Jadad score scale and Newcastle-Ottawa scale(NOS)score.The Revman 5.3 software was used for meta-analysis.Results:A total of 8 litera-tures were included,and the risk of the included literatures mainly came from the allocation hiding and out-come blind methods after evaluated with the Cochrane risk bias assessment tool;The Jadad scale scores of the 6 randomized controlled studies and the NOS scores of the 2 cohort studies were all ≥ 5.A total of 170 subjects were included,including 91 dogs,50 rabbits,and 29 clinical patients;In the animal experiments of dogs,the SCBF increased when the spinal vertebrae were shortened by 2/4 compared with 1/3 or 1/4[OR=-24.10,95％CI(-35.96,-12.23),Z=3.98,P＜0.0001];The SCBF in dogs decreased when the spinal vertebrae were shortened by 2/3 or 3/4 compared with 2/4[OR=44.63,95％CI(19.16,70.09),Z=3.43,P=0.0006];Spinal cord evoked potentials(SCEP)was significantly abnormal when spinal vertebrae shortening was 2/3 or 3/4 compared with 1/3 or 1/4[OR=0.03,95％CI(0.00,0.21),Z=3.55,P=0.004];The dural sac tortuous angle in-creased significantly when the spinal vertebrae shortening in rabbits was more than 2/4[OR=53.51,95％CI(17.92,89.10),Z=2.95,P=0.003],which led to a sharp decrease in SCBF,and the difference was statistically significant.In clinical studies,the SCBF after spinal vertebrae shortening of less than 2/4,that was,about 2/4 of the resection space,was slightly higher than that after vertebral column resection(VCR)[OR=43.81,95％CI(20.40,67.21),Z=3.67,P=0.002],and the difference was statistically significant.Conclusions:In animal ex-periments in dogs and rabbits and clinical studies,spinal vertebrae shortening of less than 2/4 is the safe range of osteotomy;In the animal experiment of dogs,when the shortening is more than 2/3 or 3/4,it will lead to a sharp decrease in SCBF and cause obvious SCEP abnormalities.

Patients with advanced pregnancy complicated by acute ST-segment elevation myocardial infarction are relatively rare both domestically and internationally,and there are currently no relevant guidelines to guide clinical treatment.In this case,a 39-year-old pregnant woman was admitted to the hospital with sudden chest pain,and the electrocardiogram showed extensive anterior ST-segment elevation myocardial infarction.Coronary angiography showed subtotal subtotal occlusion of the proximal left anterior descending artery.Reperfusion and revascularization were given,and the blood flow grade of the trial of thrombolytic in myocardial infarction was restored.Complete intravascular ultrasonography to determine the cause of occlusion due to spontaneous hematoma of the left anterior descending artery.After the operation,a reasonable antiplatelet and anticoagulant treatment regimen was selected according to the coronary artery lesion,and the pregnancy was terminated at the appropriate time,and 1 live male baby was successfully delivered.Maternal and fetal health was followed up after 1、3 and 6 months.Through the experience and summary of the treatment process,combined with the literature,the pathogenesis of this disease is discussed,and the strategy of revascularization,the selection of antithrombotic drugs and the timing of pregnancy termination are discussed in depth for clinical reference.