Objective: To compare the in vitro quality differences of leukoreduced pooled concentrated platelets prepared from whole blood preserved at different temperatures and for various durations, determine the safe time window for refrigerated whole blood in platelet preparation, and provide experimental evidence for optimizing blood component preparation procedures and improving the comprehensive utilization rate of blood resources. Methods: A total of 324 units of 400 mL ACD-B anticoagulated whole blood were randomly divided into two groups and stored at 4℃ and 22℃, respectively. The buffy coat was separated at three time intervals: <6 h, 6-12 h, and >12 h (≤18 h) post-collection, and allowed to rest overnight at 22℃. On the following day, the buffy coats from each group were pooled to prepare leukoreduced pooled platelet concentrates (LPPCs). Cell counts were performed, and metabolic parameters including pH, glucose, and lactate levels were measured to evaluate metabolic status. Platelet in vitro function and activation were assessed by thromboelastography (TEG), platelet aggregation rate, and the expression of PAC-1 and CD62P. The differences between the two groups were compared. Results: For pooled concentrated platelets prepared from whole blood stored at 4℃ and 22℃ for <6 h and 6-12 h, there were no significant differences in platelet count, pH, glucose levels, lactic acid levels, thromboelastography (TEG), platelet aggregation rate, or platelet activation rate (P>0.05). With prolonged refrigeration time of whole blood, compared with pooled concentrated platelets prepared from whole blood stored at 22℃ for >12 h but ≤18 h, those prepared from whole blood stored at 4℃ for >12 h but ≤18 h showed a decreased platelet count (1 152.83±180.08 vs 1 368.83±134.86, P=0.040), a significantly increased ADP-induced aggregation rate (26.82±6.59 vs 13.88±10.21, P=0.030), and significantly elevated expression rates of PAC-1 and CD62P (72.64±6.74 vs 63.28±5.97, P=0.030). However, there were no significant differences in pH, glucose content, lactate content, or thromboelastography (P>0.05). Conclusion: There was no significant difference in the in vitro count, function, or activation of pooled concentrated platelets prepared from whole blood stored at 4℃ and 22℃ within 12 hours. However, statistically significant differences were observed between the mixed concentrated platelets prepared from whole blood stored at 4℃ and those stored at 22℃ for more than 12 hours but not exceeding 18 hours. These findings can provide a reference for the preparation methods and clinical application of refrigerated platelets.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveTo characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective To investigate the effects of microRNA-34a(miR-34a-5p)on the progression of chronic lymphocytic leukemia(CLL)through the Wnt/β-catenin signaling pathway.Methods Human chronic B-cell leukemia MEC-1 cells were selected for experimentation.MEC cells were divided into two groups,group one:the p53 agonist group and the control group;group two:the control group,the miR-34a-5p mimic group and its corresponding negative control,the miR-34a-5p inhibitor group and its corresponding negative control,as well as the miR-34a-5p inhibitor+Wnt inhibitor XAV-939 group.The expression levels of miR-34a-5p in each group were measured using real-time fluorescence quantitative PCR(qPCR).Cell proliferation was assessed by CCK-8 assay,while cell migration ability was evaluated using Transwell migration assay.Dual-luciferase reporter assay was employed to validate the targeting relationships between p53 and miR-34a-5p,as well as between miR-34a-5p and Wnt1.Western blot analysis was used to detect the protein expressions of β-catenin and Cyclin D1,which were key components of the Wnt/β-catenin signaling pathway.Results In MEC-1 cells:① compared with the control group,there was a increased miR-34a-5p expression and inhibited cell proliferation in the p53 agonist group(P＜0.05).Dual-luciferase reporter assay confirmed a negative regulatory correlation between miR-34a-5p and p53.② the miR-34a-5p mimic group showed significantly upregulated miR-34a-5p expression compared to the control group,leading to suppressed cell proliferation,reduced migration capability and decreased protein expressions of β-catenin and Cyclin D1(P＜0.05).Conversely,the miR-34a-5p inhibitor group demonstrated significantly downregulated miR-34a-5p expression,resulting in enhanced cell proliferation,increased migratory capacity and upregulated protein levels of β-catenin and Cyclin D1 compared to those of the control group(P＜0.05).③ A targeting relationship was observed between miR-34a-5p and Wnt1.④ Compared with the miR-34a-5p inhibitor group,the XAV-939 group exhibited significantly upregulated miR-34a-5p expression,markedly decreased numbers of migrated cells and substantially reduced protein expression levels of β-catenin and Cyclin D1(P＜0.05).Conclusion miR-34a plays the role of a tumor suppressor gene in CLL.Overexpression of miR-34a can inhibit the Wnt/β-catenin signaling pathway,reduce the proliferation activity and migration ability of cells,and promote cell apoptosis.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

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.