Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

OBJECTIVE To explore the anti-inflammatory and antifungal action mechanism of taste-masked Lithospermum Saf-flower emulsion in vivo and in vitro.METHODS In vitro,the anti-inflammatory effect was detected by MTT assay,qPCR and ELISA.The anti-fungal effect of the product was investigated by broth dilution experiment,bactericidal kinetics,germ tube inhibition and XTT reduction test.In vivo,the effect was evaluated and the mechanism was investigated on the skin disease model of Candida al-bicans in mice.RESULTS Lithospermum in taste-masked Lithospermum Safflower emulsion had a significant inhibitory effect on the proliferation of RAW264.7 cells,and Safflower inhibited the production of IL-6 induced by LPS in a dose-dependent manner.Litho-spermum significantly inhibited the activity of Candida albicans,and its bactericidal mode is time-and concentration-dependent;Lithospermum significantly reduced the formation of Candida albicans germ tubes and destroyed its biofilm;Safflower had no direct kill-ing effect on Candida albicans,was not able to inhibit its biofilm formation,but significantly reduced the hyphal growth of Candida al-bicans and increased its ROS level.CONCLUSION The combination of Lithospermum and Safflower in the taste-masked Lithosper-mum Safflower emulsion can work synergistically to reduce inflammatory damage and treat Candida albicans infection of the skin.

[Abstract] [Objective] To assess the effect of a centrifugal haemocyte separator on platelet counts in patients with neurological immune-mediated disorders during/after therapeutic plasma exchange (TPE). [Methods] This study included 189 patients (108 females and 81 males) who were treated in the department of neurology at Huashan Hospital, Fudan University, from March 2021 to March 2022. A total of 820 TPE treatments were carried out. Each patient received 2 to 5 TPEs, with each TPE amounting to the patient's plasma volume. The peripheral blood cell counts of the patients were evaluated before TPE and after 2 to 5 TPEs. [Results] The duration of a single TPE in this study was 94(84,107) minutes, and the actual volume of a single TPE replacement was 2 456(2 142, 2 785) mL. The number of patients who underwent TPE for 2, 3, 4, and 5 sessions was 17, 28, 18, and 126, respectively. The platelet (PLT) counts of the patients before and after the TPE were 195×10⁹/L (range:150 to 245) and 220×10⁹/L (range:170 to 270), respectively (P<0.05). Consequently, the overall PLT counts exhibited a significant decrease from baseline following TPE, yet the PLT counts remained within the normal range after TPE. Spearman's correlation analysis indicated that platelet loss did not correlate with the duration of TPE (ρ=0.037), the age of the patient (ρ=0.015), or the volume of the single replacement fluid (ρ=0.034), P>0.05, weakly correlated with the number of TPE sessions (ρ=0.017), and moderately correlated with the PLT counts before TPEs (ρ=0.446). [Conclusion] The TPE procedure exhibited a measurable impact on the patients' platelet levels, but the platelet counts remained within the normal range, therefore did not interfere with the patients' subsequent treatment protocols. The decrease in platelet level was correlated with the baseline platelet level before treatment and the number of TPE sessions.

Objective To investigate the impact of exosomal miRNAs derived from endoplasmic reticulum-stressed(ERS)head and neck squamous cell carcinoma(HNSCC)cells on macrophages.Methods This study was reviewed and approved by the Ethics Committee.The expression levels of ERS-associated proteins,including protein kinase R-like endoplasmic reticulum kinase(PERK)and glucose-regulated protein 78(GRP78),in HNSCC tissues and para-tumor tissues were detected by Western blot(WB)and quantitative real-time PCR(RT-qPCR).HN4 human laryngeal squamous cell carcinoma cells were treated with 500 U/mL interferon-γ(IFN-γ)for 48 h to induce ER stress,and exo-somes secreted by ER-stressed HN4 cells were collected and identified.The types of miRNAs in exosomes were identi-fied through bioinformatics analysis,and the target genes of miRNAs were predicted.Macrophages were transfected with miRNA,co cultured with collected exosomes,and the expression of PTEN in macrophages was knocked down.The downstream signaling pathway regulated by exosomal miRNAs was studied by WB and RT-qPCR.Results Compared with that in para-tumor tissues,the expression level of ER stress-associated proteins in HNSCC tissues was increased(P＜0.05).RNA-seq analysis revealed that miR-26a-5p was highly upregulated in ER-stressed HN4 cell-derived exo-somes(P＜0.05).PTEN is the target gene for miR-26a-5p.miR-26a-5p increased the expression level of PD-L1 in mac-rophages and downregulated the expression of PTEN(P＜0.05).Macrophages co cultured with ERS extracellular vesi-cles showed an increase in miR-26a-5p and PD-L1 expression,a decrease in PTEN expression,and an increase in p-AKT expression(P＜0.05).Knock down the expression of PTEN in macrophages and increase the expression of PD-L1(P＜0.01).Conclusion ERS HNSCC cell-derived exosomal miR-26a-5p promotes the expression of PD-L1 in macro-phages through the PTEN/AKT signaling pathway.

Objective To explore the toxicity of Polygonum multiflorum alcohol extract on 3D hepatospheres.Methods Variations in culture conditions and cell ratios were implemented,followed by the assessment of cell sphere diameter,density,and roundness,aiming to explore the optimal culture conditions.The 3D hepatocyte spheres were divided into control group and experimental-L,-M,-H groups.The experimental-L,-M,-H groups were treated with 0.25,1.00 and 2.50 mg·mL-1 Polygounm multiforum alcohol extract,and the control group was given the same amount of culture medium.The cell viability of the cell spheroids was tested by CellTiter-Glo reagent,the expression level of liver function related genes was detected by fluorescent quantitative polymerase chain reaction(RT-qRCR).The toxicity of cell spheres was detected by double fluorescent staining of living and dead cells.Results The ideal culture condition of cell sphere was 500 cells per micropore,and the cell ratio was HepG2-Huvec-LX-2=8∶1∶1.It displayed the values of 0.91±0.07 for circularity,0.91±0.02 for firmness,1.12±0.14 for aspect ratio,and(170.97±14.79)μm for diameter.On the 3rd,7th,10th and 14th days,the expression levels of albumin(ALB)mRNA were 1.00±0.02,0.96±0.02,0.54±0.07,0.52±0.07,and the expression levels of cytochrome P450 1A2(CYP1A2)mRNA were 1.00±0.10,2.15±0.16,2.45±0.33,1.30±0.03,respectively.The expression levels of multidrug resistance protein 2(MPR2)in the control group and the experimental-L,-M,-H groups were 1.00±0.31,1.38±0.24,1.48±0.06 and 1.90±0.08,respectively;spheroid viability were(98.19±0.49)％,(88.53±0.90)％,(71.60±2.91)％and(56.65±5.41)％.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the control group(all P＜0.05).Conclusion The established hepatocyte sphere co-culture model showed varying degrees of expression of phase Ⅰ/Ⅱ drug metabolism enzymes,transporters,and liver cell specific marker molecule albumin and can be used to evaluate the toxicity of multiflorum multiflorum,which provides further reference for the clinical application of multiflorum multiflorum.

Objective To investigate the correlation between the glucose time in range(TIR)and left ventricular mass index(LVMI)in the patients with type 2 diabetes mellitus(T2DM)complicating hyperten-sion.Methods A total of 102 inpatients with T2DM in the Mingguang Municipal People's Hospital from January to December 2022 were selected as the study subjects and conducted the continuous dynamic glucose monitoring.They were divided into the group A(TIR≤40％,n=31),group B(TIR＞40％-70％,n=41)and group C(TIR＞70％,n=30)according to the TIR level.The clinical data,laboratory indicators and echo-cardiographic parameters were collected and compared among the three groups.Results Compared with the group A,the age,disease course,systolic blood pressure and the levels of HbA1c,FPG,SCr and TG in the group C were significantly decreased,the HDL-C level was increased,and the differences were statistically sig-nificant(P＜0.05).Compared with the group B,the age and the levels of SCr,TG,HDL-C,HbA1c and FPG in the group C were decreased,and the differences were statistically significant(P＜0.05).Compared with the group A and group B,LAD,LVPW,IVS and LVMI in the group C were reduced with statistical differences(P＜0.05).The multiple linear stepwise regression analysis results showed that TIR was a protective factor for LVMI(OR=0.562,95％CI 0.413-0.673,P＜0.05),and the disease course and systolic blood pressure were the risk factors(OR=1.511,95％CI:1.067-2.947;OR=2.325,95％CI:1.086-5.574,P＜0.05).Conclusion TIR in the patients with T2DM complicating hypertension is correlated with LVMI,and the TIR level may be an influencing factor for early cardiovascular events.

Objectives: Blood and urine are commonly used specimens for clinical testing, and their contents, particularly exosomal microRNA (miRNA), are diverse, reflecting the metabolic activities of tissues and organs in the body. Methods: Blood and urine samples were collected from six healthy adults. Exosomes were then enriched from these samples, followed by sequencing and bioinformatic analysis of exosomal miRNA. Results: The comparative analysis of miRNAs in blood and urine revealed that 41 miRNAs were more abundant in blood, while 61 were found at lower levels. Notably, hsa-miR-934 was among those with higher expression in blood, whereas hsa-miR-425-5p was one of the miRNAs with lower expression.Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the target mRNAs of differentially expressed exosomal miRNAs (DEexo-miRNAs) in both blood and urine are implicated in various signaling pathways, including proteoglycans in cancer, axonal guidance, and the regulation of the actin cytoskeleton. Additionally, the target mRNAs associated with DEexo-miRNAs in urine were also linked to processes such as ubiquitin-mediated proteolysis and the phosphatidylinositol signaling system. In contrast, the target mRNAs corresponding to DEexo-miRNAs in blood were involved in the FoxO signaling pathway and chronic myeloid leukemia, among others. Conclusion This study observed differential expression of exosomal miRNAs in blood and urine, thereby enriching the available library of exosomal miRNA for these two sample types. It also lays the groundwork for the detection of exosomal biomarkers from blood and urine.

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients’ factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men’s Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: “low libido”, “erectile dysfunction”, “ejaculatory dysfunction”, “premature ejaculation”, “retrograde ejaculation”, “delayed ejaculation”, “anejaculation”, and “orgasmic dysfunction” between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socioeconomic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient’s individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.