ObjectiveTo explore the effectiveness and potential mechanism of Shugan Jianpi Granules （疏肝健脾颗粒） combined with Chushi Zhiyang Ointment （除湿止痒软膏） in the treatment of atopic dermatitis with sleep disturbance of liver constraint and spleen deficiency syndrome. MethodsSixty-six patients with atopic dermatitis combined with sleep disturbance of liver constraint and spleen deficiency syndrome were randomly divided into 33 cases each in the treatment group and the control group. Both groups were treated with Chushi Zhiyang Ointment for external use. The treatment group additionally received Shugan Jianpi Granules orally， one dose per day； and the control group received cetirizine hydrochloride tablets orally， 10mg per day， taken before bedtime. Both groups were under the treatment for 4 weeks. Clinical effectiveness was evaluated after treatment， and the SCORing Atopic Dermatitis （SCORAD） index， pruritus visual analog scale （VAS） score， Insomnia Severity Index （ISI） score， and Pittsburgh Sleep Quality Index （PSQI） score were recorded before and after treatment， and serum levels of melatonin （MLT）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-13 （IL-13）， and tumor necrosis factor-α （TNF-α） were measured. The patients were also tested for blood routine， liver function and kidney function before and after treatment， and the occurrence of adverse events was also observed. ResultsThe total effective rate in the treatment group （90.63%， 29/32） was significantly higher than that in the control group （66.67%， 20/30， P＜0.05）. After the interventions， the scores for SCORAD， VAS， ISI， and PSQI， as well as the levels of IL-4， IL-6， IL-13， and TNF-α， were significantly reduced in both groups. In contrast， the MLT levels in treatment group significantly elevated compared to that before treatment （P＜0.05）. Comparing between the two groups after treatment， the scores of SCORAD， ISI， PSQI， and VAS， as well as the levels of serum IL-4 and IL-13 in the treatment group were significantly lower than those in the control group， while the MLT levels were markedly higher than that in the control group （P＜0.05 or P＜0.01）. There was no obvious abnormality in blood routine， liver function and kidney function in both groups when compared before and after treatment. The incidence rate of adverse reactions was 9.38% （3/32） in the treatment group and 13.33% （4/30） in the control group， and the difference between groups showed no statistical difference （P＞0.05）. ConclusionOn the basis of topical application of Chushi Zhiyang Ointment， the combined application of Shugan Jianpi Granules can significantly alleviate the degree of skin lesions and itching， and improve the quality of sleep in atopic dermatitis patients with sleep disturbance of liver constraint and spleen deficiency syndrome， and its mechanism may be related to regulating the immune balance， reducing the secretion of inflammatory factors， and elevating the level of MLT.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

Post-orgasmic illness syndrome (POIS) is a rare condition characterized by the rapid onset of extreme fatigue, flu-like symptoms, difficulty concentrating, depression, nasal congestion, rhinorrhea, itchy eyes, and other physical and psychological discomforts following ejaculation. This report presents the outcomes of two patients with POIS who underwent a two-year course of autologous seminal plasma subcutaneous cluster immunotherapy. Treatment efficacy was assessed using methods such as the symptom Visual Analogue Scale (VAS), the Union Physio-Psycho-Social Assessment Questionnaire (UPPSAQ)-70, and the Short Form 36 Health Survey (SF-36). The results suggest that autologous seminal plasma subcutaneous cluster immunother-apy may be a safe and effective therapeutic approach for POIS.

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*