OBJECTIVE:Disorders in iron metabolism increase the risk of type 2 diabetes mellitus.Hepcidin play an important role in maintaining iron homeostasis in the body,but its level increases with increased inflammation.Changes in hepcidin and iron homeostasis and the extent of their association with inflammation in people with and without type 2 diabetes mellitus are unknown.Meta-analysis was used to evaluate the effect of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus.METHODS:CNKI,PubMed,Web of Science and EBSCOhost databases were searched by computer to collect observational studies related to inflammatory index and hepcidin in patients with type 2 diabetes mellitus.The search time was from September 1,2000 to September 30,2024.Three researchers independently screened the literature,extracted data and evaluated the quality of the included literature.Meta-analysis was performed by Review Manager 5.3,Stata 17.0 and GraphPad Prism 8.0.2 software.RESULTS:A total of 15 articles(17 studies)involving 3 159 participants,including 1 357 patients with type 2 diabetes mellitus,were included.Meta-analysis results showed that compared with the control group,patients with type 2 diabetes mellitus had higher levels of serum hepcidin[standardized mean difference(SMD)=0.35,95％confidence interval(CI)(0.05,0.65),P＜0.05],serum ferritin(SMD=0.49,95％CI(0.21,0.78),P＜0.01)and serum transferrin(SMD=0.19,95％CI(0.00,0.37),P＜0.05).Subgroup analysis results indicated that inflammation had a significant effect on serum hepcidin(SMD=0.76,95％CI(0.17,1.34),P＜0.05)and serum ferritin(SMD=0.77,95％CI(0.06,1.47),P＜0.05)in patients with type 2 diabetes mellitus.CONCLUSION:Hepcidin concentration is positively correlated with type 2 diabetes mellitus.Inflammation is one of the risk factors of type 2 diabetes mellitus.Early prevention of inflammation has certain significance in preventing iron metabolism disorder in patients with type 2 diabetes mellitus.

ObjectiveTo optimize and validate the optimal sequential alcohol-water extraction process of modified Banxia Xiexintang（MBXT） based on pharmacodynamic evaluation， combined with the G1-entropy weight method and Box-Behnken response surface methodology， and to systematically and comprehensively analyze the material basis of this formula， providing a scientific basis for its quality control and industrial production. MethodsRats were randomly divided into the normal group， model group， metformin group， and MBXT water extraction， water extraction and ethanol precipitation， sequential ethanol-water extraction groups. Except for the normal group， a polycystic ovary syndrome with insulin resistance（PCOS-IR） model was established in all rats via a high-fat diet combined with letrozole induction. Enzyme-linked immunosorbent assay（ELISA） biochemical assay kits and hematoxylin-eosin（HE） staining were used to compare sex hormone levels in serum and ovarian histopathology， thereby screening extraction process routes. Based on this， a comprehensive score was constructed using the G1-entropy weight method based on the transfer rates of index components（berberine hydrochloride and baicalin） and the dry extract rate. Box-Behnken response surface methodology was then utilized to optimize the extraction process parameters. Finally， the chemical constituents of the sample from the optimal process were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS）. ResultsPharmacodynamic findings revealed that compared with the normal group， serum testosterone（T） and luteinizing hormone（LH） levels were significantly elevated in the model group， while estradiol（E₂） and follicle-stimulating hormone（FSH） levels were significantly decreased（P<0.01）， with polycystic changes observed in ovarian tissues. Compared with the model group， all treatment groups significantly reversed the changes in sex hormone levels， with the sequential ethanol-water extraction group showing the optimal effect in improving the aforementioned indicators and pathological morphology， followed by subsequent process optimization. The optimized process involved adding 12 times the amount of 70% ethanol for extracting twice， each lasting 120 min， and adding 12 times the amount of water for extracting thrice， each lasting 90 min. Validation test results showed that under optimal process conditions， the average transfer rates of berberine hydrochloride and baicalin were 76.05% and 93.38%， respectively. MS analysis identified a total of 377 compounds， including 112 flavonoids， 41 terpenoids， 28 organic acids， 22 coumarins， and 8 alkaloids， while elucidating the cleavage patterns of key components. ConclusionThe optimized sequential ethanol-water extraction process is stable and feasible， effectively preserving the material basis of MBXT for treating PCOS-IR. It further clarifies the main chemical composition of this formula， providing a scientific basis for the development and quality control of its preparations.

ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

OBJECTIVE:Disorders in iron metabolism increase the risk of type 2 diabetes mellitus.Hepcidin play an important role in maintaining iron homeostasis in the body,but its level increases with increased inflammation.Changes in hepcidin and iron homeostasis and the extent of their association with inflammation in people with and without type 2 diabetes mellitus are unknown.Meta-analysis was used to evaluate the effect of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus.METHODS:CNKI,PubMed,Web of Science and EBSCOhost databases were searched by computer to collect observational studies related to inflammatory index and hepcidin in patients with type 2 diabetes mellitus.The search time was from September 1,2000 to September 30,2024.Three researchers independently screened the literature,extracted data and evaluated the quality of the included literature.Meta-analysis was performed by Review Manager 5.3,Stata 17.0 and GraphPad Prism 8.0.2 software.RESULTS:A total of 15 articles(17 studies)involving 3 159 participants,including 1 357 patients with type 2 diabetes mellitus,were included.Meta-analysis results showed that compared with the control group,patients with type 2 diabetes mellitus had higher levels of serum hepcidin[standardized mean difference(SMD)=0.35,95％confidence interval(CI)(0.05,0.65),P＜0.05],serum ferritin(SMD=0.49,95％CI(0.21,0.78),P＜0.01)and serum transferrin(SMD=0.19,95％CI(0.00,0.37),P＜0.05).Subgroup analysis results indicated that inflammation had a significant effect on serum hepcidin(SMD=0.76,95％CI(0.17,1.34),P＜0.05)and serum ferritin(SMD=0.77,95％CI(0.06,1.47),P＜0.05)in patients with type 2 diabetes mellitus.CONCLUSION:Hepcidin concentration is positively correlated with type 2 diabetes mellitus.Inflammation is one of the risk factors of type 2 diabetes mellitus.Early prevention of inflammation has certain significance in preventing iron metabolism disorder in patients with type 2 diabetes mellitus.

Objective:To conduct signal detection and analysis of cardiovascular-related adverse events associated with second-generation H1 antihistamines(sgAH)in the elderly population, utilizing the Food and Drug Administration adverse event reporting system(FAERS)database.The findings provide a reference for assessing the clinical drug safety of sgAH in the elderly.Methods:A cross-sectional study was conducted.Four methods were utilized to detect signals of cardiovascular-related adverse events associated with sgAHs in the FAERS database, covering the period from the first quarter of 2004 to the first quarter of 2024.These methods included the reporting odds ratio, the Medicines and Healthcare Products Regulatory Agency method, the Bayesian Confidence Propagation Neural Network method, and the multi-item gamma Poisson shrinker method.Subgroup analyses were performed on both the overall population and the elderly population(aged ≥65).Results:A total of 1 065 reports of cardiovascular-related adverse events involving sgAHs such as loratadine, desloratadine, cetirizine, levocetirizine, and fexofenadine were collected.In the overall population, palpitations were identified as a positive signal, while desloratadine also demonstrated positive signals for tachycardia and prolonged electrocardiogram QT interval.In the elderly population, both palpitations and prolonged electrocardiogram QT interval were recognized as positive signals, exhibiting higher information component(IC)values and empirical Bayesian geometric mean(EBGM)values compared to the overall population.Furthermore, loratadine and desloratadine were also identified as positive signals for prolonged electrocardiogram QT interval in the elderly.Conclusions:Palpitations have been identified as a significant indicator of cardiovascular-related adverse events associated with sgAHs.Elderly patients should be particularly vigilant regarding the risk of prolonged QT intervals on electrocardiograms.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.

OBJECTIVE: To investigate the effectiveness of knee arthroscopy with wire anchor nailing composite double pulley technique in the treatment of anterior cruciate ligament (ACL) tibial avulsion fracture involving the anterior root of the lateral meniscus (LM). METHODS: Clinical data of 35 patients with ACL tibial avulsion fracture involving the anterior root of the LM admitted between January 2019 and September 2023 and met the selection criteria were retrospectively analysed. There were 20 males and 15 females; ages ranged from 10 to 57 years, with a mean of 29 years. The time from injury to surgery ranged from 3 to 20 days, with a mean of 9.6 days. Meyers-McKeever classification included 5 cases of type Ⅱ, 12 cases of type Ⅲ, and 18 cases of type Ⅳ. Preoperative anterior knee instability Lachman test and anterior drawer test were positive. The anterior root of the LM as well as the avulsion fracture block were fixed using suture anchor nails compounded with double pulley technique under arthroscopy. Postoperative X-ray films were performed to assess fracture healing; knee stability was assessed using the anterior drawer test and Lachman test, anterior laxity of the knee was measured by KT-2000, and knee function was assessed using the Lysholm score and the International Knee Documentation Committee (IKDC) score; at last follow-up, the recovery of the meniscus was assessed using the McMurry test and knee hyperextension test. RESULTS: All the patients were successfully operated, the operation time ranged from 56 to 78 minutes,with an average of 67.6 minutes, and there was no nerve or blood vessel injury during operation. Thirty-five cases were followed up 12-18 months with an average of 15.1 months. During the follow-up, there was no infection, knee stiffness, loosening of internal fixation, fracture displacement, or re-fracture. The fractures all healed, with a clinical healing time of 8-15 weeks, averaging 10.9 weeks. At last follow-up, 4 patients had weakly positive anterior drawer test and Lachman test, and the rest were negative; McMurry test and knee hyperextension test were negative; no patient complained of knee extension pain or straightening obstacles, and all the patients resumed their normal life or sports and labour; 16 patients with unclosed epiphyses did not have any epiphyseal injuries or growth disorders. Lysholm score, IKDC score, and KT-2000 anterior knee laxity at last follow-up significantly improved when compared with preoperative ones ( P<0.05). CONCLUSION The treatment of ACL tibial avulsion fracture involving the anterior root of the LM with suture anchor composite double pulley technique can effectively fix the anterior root of the LM while fixing the avulsion fracture block, and better restore the function and stability of the knee joint.
Humans ; Male ; Female ; Adult ; Arthroscopy/methods* ; Adolescent ; Retrospective Studies ; Tibial Fractures/surgery* ; Young Adult ; Middle Aged ; Fractures, Avulsion/surgery* ; Fracture Fixation, Internal/instrumentation* ; Anterior Cruciate Ligament Injuries/surgery* ; Child ; Treatment Outcome ; Suture Anchors ; Menisci, Tibial/surgery* ; Tibial Meniscus Injuries/surgery* ; Bone Nails ; Knee Joint/surgery*

OBJECTIVES: To evaluate the feasibility, efficacy and safety of Sentinel cerebral embolic protection device (CEPD) during transcatheter aortic valve replacement (TAVR). This study is a subgroup analysis of the China Moderate to Severe Valvular Heart Disease Registry, which has been registered at the Chinese Clinical Trial Registry (ChiCTR2300075006). METHODS: Patients undergoing TAVR with the Sentinel CEPD from October 2023 to September 2024 were retrospectively enrolled. A total of 80 patients were included, with a median age of 72 (68, 76) years, including 52 males (65.0%) and 28 females (35.0%); 62 patients (77.5%) with tricuspid valves, and 18 patients (22.5%) with bicuspid valves; 34 patients (42.5%) with type Ⅰ aortic arch, 24 patients (30.0%) with type Ⅱ aortic arch, 12 patients (15.0%) with type Ⅲ aortic arch, and 10 patients (12.5%) with bovine-type aortic arch. Clinical data of the patients were summarized and analyzed. The primary endpoints were success rate of Sentinel CEPD implantation, as well as all-cause death, symptomatic stroke, transient ischemic attack, and Sentinel CEPD access vessel complications during hospitalization and within 30 days postoperatively. RESULTS: In the 80 patients, self-expanding valves were used in 68 cases (85.0%) and balloon-expandable valves in 12 cases (15.0%). Seventy-nine patients (98.8%) successfully underwent TAVR with Sentinel CEPD deployment. Macroscopically visible debris was captured in 92.5% (74/80) by filters of Sentinel CEPD. Although the procedure time for Sentinel CEPD placement was slightly longer in patients with bovine-type aortic arch, there was no statistically significant difference in deployment time among different aortic arch types (P>0.05). During hospitalization and within 30 days postoperatively, only one case of transient ischemic attack occurred, and there was no all-cause mortality, symptomatic stroke, or access-site vascular complications related to the Sentinel CEPD observed. CONCLUSIONS The Sentinel CEPD demonstrates high feasibility across aortic arch types, potential efficacy in embolic capture, and excellent safety in TAVR.
Humans ; Transcatheter Aortic Valve Replacement/adverse effects* ; Male ; Female ; Aged ; Embolic Protection Devices ; Retrospective Studies ; Intracranial Embolism/prevention & control* ; Aged, 80 and over ; Aortic Valve Stenosis/surgery* ; Aortic Valve/surgery*

Objective We explored the anti-depressant activity and mechanism of arecoline in vivo in a mouse model of depression induced by chronic unpredictable mild stress.The aim was to explore the possible mechanisms of action,providing experimental evidence for further research into the health benefits of arecoline and theoretical support for the scientific development and utilization of this resource.Methods Sixty quarantine-qualified SPF C57BL/6J mice were divided randomly into a control group,model group,fluoxetine group(20 mg/kg),and arecoline low-,medium-,and high-dose groups(10,20,and 40 mg/kg,respectively)according to body mass(n=10 mice per group).The effects of arecoline on the behavior of the mice were evaluated by open-field,tail-suspension,and forced-swimming tests.Serum corticosterone and serum and brain levels of superoxide dismutase(SOD)were detected by enzyme-linked immunoassay.Malondialdehyde(MDA),catalase(CAT),5-hydroxytryptamine(5-HT),and norepinephrine(NE)levels in brain tissue,and dopamine(DA),gamma-aminobutyric acid(GABA),tumor necrosis factor(TNF-α),interleukin(IL)-10,IL-1β,brain-derived neurotrophic factor(BDNF),tropomyosin receptor kinase B(TrkB),and cAMP-response element binding protein(CREB)were detected by Western Blot.Results Arecoline significantly reduced the total distance and average speed of the model mice in open field tests and increased activities,and significantly reduced the immobility time in the tail suspension and forced swimming tests.Arecoline also significantly decreased serum corticosterone levels,increased SOD and CAT,and decreased MDA levels.5-HT,DA,NE,and GABA levels were significantly increased,and the cytokines TNF-α,IL-6,and IL-1β were significantly decreased.Expression levels of BDNF,TrkB,and CREB in the brain tissue were significantly increased.Conclusions Research has found that arecoline has a significant antidepressant ability,and its mechanism may be achieved by reducing oxidative stress damage,inhibiting neuroinflammation,regulating neurotransmitter balance,and regulating the BDNF/TrkB/CREB signaling pathway..This study explored the antidepressant efficacy of arecoline and preliminarily revealed its possible regulatory mechanism,which can provide data support for the neuroactivity of arecoline and lay a theoretical foundation for the development of arecoline as medicine.