Objective:To investigate the expression of placenta expressed transcript 1(Plet1)in ovarian tissue of the letrozole-induced model rats of polycystic ovary syndrome(PCOS)and its effect on the proliferation of rat ovarian granulosa cells,and to clarify the possible mechanism by which Plet1 may contribute to the pathogenesis of PCOS.Methods:The ovarian tissue samples from the rats collected in previous studies were used and divided into control and PCOS groups.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of Plet1 mRNA and protein in ovarian tissue of the rat in two groups.Additionally,twenty-four rats underwent vaginal smear cytology were divided into four groups by estrous cycle phase:proestrus,estrus,metestrus and diestrus.RT-qPCR was used to detect the expression level of Plet1 mRNA in ovarian tissue of the rats in various groups,and immunohistochemistry(IHC)method was used to detect the location of Plet1 expression in the rat ovarian tissue in various groups.The rat ovarian granulosa cells were transfected and divided into control group,si-Plet1-rat-266 group,si-Plet1-rat-383 group,and si-Plet1-rat-554 group.Cell counting kit-8(CCK-8)method was used to assess the cell proliferation activities of rat ovarian granulosa cells in various groups,and RT-qPCR method was used to detect the expression levels of cyclin-d epend ent kinase 6(CDK6)and P53 mRNA in rat ovarian granulosa cells in various groups.Results:The RT-qPCR results revealed that Plet1 mRNA was expressed in the ovaries of normal rats,while no statistically significant difference was observed across estrous cycle phases(P＞0.05).The immunohistochemistry results showed that the expression of Plet1 protein was mainly localized in ovarian granulosa cells and luteal cells in the rat ovarian tissue.Compared with control group,the expression levels of Plet1 mRNA and protein in ovarian tissue of the rats in PCOS group were significantly decreased(P＜0.05).The RT-qPCR results showed that compared with control group,the expression level of Plet1 mRNA in ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.01),exhibiting the most pronounced reduction.Compared with control group,the proliferation activity of rat ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.05).Compared with control group,the expression levels of CDK6 and P53 mRNA in rat ovarian granulosa cells in si-Plet1-rat-383 group were significantly decreased(P＜0.05 or P＜0.01).Conclusion:Plet1 protein is predominantly expressed and localized in granulosa cells and luteal cells in normal rat ovarian tissue.Its expression is downregulated in the ovarian tissue of PCOS model rats,and interference with Plet1 gene expression may inhibit the proliferation of rat ovarian granulosa cells.

Objective:To establish a detection method for fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.Methods:The detection of fatty acid composition involves pre-test of the sam-ple using the methanol sodium methylation method,followed by direct injection analysis using gas chromatography,and finally calculating the content of each fatty acid composition using the area normalization method with correction factors.The detection of methoxylaniline value is achieved by dissolving and diluting the sample with isooctane:isopropanol(8∶2,volume ratio),reacting with 4-methoxylaniline,measuring the absorbance at a wavelength of 350 nm,and calculating the methoxylaniline value.Results:Under the composition of fatty acids,the 8 kinds of fatty acids have good separation degree.The methyl ricinoleate and methyl stearate have good linear relationship in the range of 0.1-5.0 mg·mL-1.The repeatabilityand intermediate precision(RSD)ofthe determination results of each fatty acid in the sample are all less than 5%.It is also found that only α-type of linolenic acid is present in castor oil,without γ-type.In the determination of methoxyaniline value,the blank solvent does not interfere with the determination of the sample,and the repeatability RSD is 3.6%.Conclusion:The detection method for fatty acid composition and meth-oxylaniline value established in this article is accurate and reliable,and can be used for the detection of fatty acid composition and methoxylaniline value in pharmaceutical excipient castor oil.

This article reports a rare case of pantothenate kinase-associated neurodegeneration: the patient′s initial symptoms were Parkinson-like symptoms such as tremor and bradykinesia, as well as dysarthria. Brain magnetic resonance imaging showed abnormal signals in the bilateral basal ganglia region similar to the tiger′s eye sign. Two heterozygous mutations including c.803A>G(p.Asp268Gly) and c.1021C>T(p.Arg341 *) were found in the pantothenate kinase 2 gene by whole exome sequencing, and the final diagnosis was neurodegeneration with brain iron accumulation type 1, also known as pantothenate kinase-associated neurodegeneration. By reviewing the clinical characteristics, diagnostic approaches and therapeutic strategies, this article aims to enhance the recognition of this disease, avoid misdiagnosis and missed diagnosis, and provide guidance for clinical diagnosis and treatment.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

Objective:To explore the application effect of multidisciplinary graded nutritional intervention in patients with cervical cancer undergoing radiochemotherapy.Methods:A convenience sampling method was used to select 160 patients with cervical cancer who received radiochemotherapy in the First Affiliated Hospital of Wenzhou Medical University from June 2022 to June 2024. According to the order of admission, 80 patients admitted between June 2022 and June 2023 were assigned to the control group, and 80 patients admitted between July 2023 and June 2024 were assigned to the observation group. The control group received routine nutritional intervention, while the observation group received multidisciplinary graded nutritional intervention. Serum albumin, prealbumin, hemoglobin, body mass index (BMI), and Functional Assessment of Cancer Therapy-General (FACT-G) scores were compared between the two groups before and after intervention.Results:Before the intervention, there were no statistically significant differences between the two groups in serum albumin, prealbumin, hemoglobin, BMI, and FACT-G dimension scores ( P>0.05). After the intervention, serum albumin, prealbumin, hemoglobin, BMI, and FACT-G dimension scores were all higher in the observation group than in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Multidisciplinary graded nutritional intervention can improve the nutritional status and quality of life of patients with cervical cancer undergoing radiochemotherapy, and is worthy of wider application.