Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.
Humans ; Alzheimer Disease/physiopathology* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/physiology* ; Animals ; Amyloid beta-Peptides/metabolism*

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To construct a whole course management and follow-up platform, named Care Plan, for patients undergoing breast reconstruction surgery, and to evaluate its initial clinical applications.Methods:From June 2023 to January 2024, patients who underwent breast reconstruction surgery at Peking Union Medical College Hospital were selected as the study subjects and enrolled in the Care Plan platform for whole course management. The platform comprised five modules: patient education, self-assessment, medical assessment, medical follow-up, and doctor-patient dialogue, each with corresponding sub-modules and specific components. Each patient was assigned to a case manager who provided one-on-one assessment, sent patient education materials, and conducted follow-ups. The preliminary application of the Care Plan platform was evaluated based on the completeness of patient data, patient education material reading status, doctor-patient dialogue topics, and follow-up responses. At 3 months postoperatively, patients were followed up and further divided into patient education group(reading at least an article on patient educational materials) and control group based on their reading status of educational materials. Patients rated their satisfaction with the surgery using a 5-point questionnaire, including five indicators: expected breast reconstruction outcome, expected surgical type, completeness of information acquisition, breast symmetry, and breast softness. Statistical analysis was performed using SPSS 27.0.1 software, with count data expressed as frequencies and (or) percentages, normally distributed measurement data expressed as Mean±SD, intergroup comparisons conducted using t-test, and P<0.05 indicating statistical significance. Results:A total of 147 female patients aged 16 to 63 years with a body mass index of 16.6 to 31.3 kg/m 2 were ultimately included. All 147 patients completed the content of the self-assessment and medical assessment modules, with relatively complete data. Of the 133 patients who received patient education materials sent through the platform, 38 (28.6%) read the materials, with the sub-module on the introduction and choices of the reconstruction surgery (37.3%, 94/252 ) being the most frequently viewed. A total of 24 patients (16.3%, 24/147 ) raised 45 questions using the doctor-patient dialogue module, with the highest proportion related to consultation issues and complications, each accounting for 22.2% (10/45). Twenty-three patients completed the 3-month follow-up, with 12 in the patient education group and 11 in the control group. The patient education group scored higher than the control group in terms of completeness of information acquisition [(4.58±0.51) points vs. (3.91±0.70) points, t=-2.65, P=0.015], while scoring lower in breast symmetry [(3.92±0.79) points vs. (4.63±0.67) points, t=2.33, P=0.030]. There was no significant difference between the two groups in terms of expected breast reconstruction outcome, expected surgical type, and breast softness scores ( P>0.05 for all). Conclusion:The Care Plan platform for whole course management and follow-up of breast reconstruction can assist medical staff in formulating patient-centered management plans, improve patients’ understanding of surgical information, and aid patients in making decisions regarding breast reconstruction methods.

Objective:To construct a whole course management and follow-up platform, named Care Plan, for patients undergoing breast reconstruction surgery, and to evaluate its initial clinical applications.Methods:From June 2023 to January 2024, patients who underwent breast reconstruction surgery at Peking Union Medical College Hospital were selected as the study subjects and enrolled in the Care Plan platform for whole course management. The platform comprised five modules: patient education, self-assessment, medical assessment, medical follow-up, and doctor-patient dialogue, each with corresponding sub-modules and specific components. Each patient was assigned to a case manager who provided one-on-one assessment, sent patient education materials, and conducted follow-ups. The preliminary application of the Care Plan platform was evaluated based on the completeness of patient data, patient education material reading status, doctor-patient dialogue topics, and follow-up responses. At 3 months postoperatively, patients were followed up and further divided into patient education group(reading at least an article on patient educational materials) and control group based on their reading status of educational materials. Patients rated their satisfaction with the surgery using a 5-point questionnaire, including five indicators: expected breast reconstruction outcome, expected surgical type, completeness of information acquisition, breast symmetry, and breast softness. Statistical analysis was performed using SPSS 27.0.1 software, with count data expressed as frequencies and (or) percentages, normally distributed measurement data expressed as Mean±SD, intergroup comparisons conducted using t-test, and P<0.05 indicating statistical significance. Results:A total of 147 female patients aged 16 to 63 years with a body mass index of 16.6 to 31.3 kg/m 2 were ultimately included. All 147 patients completed the content of the self-assessment and medical assessment modules, with relatively complete data. Of the 133 patients who received patient education materials sent through the platform, 38 (28.6%) read the materials, with the sub-module on the introduction and choices of the reconstruction surgery (37.3%, 94/252 ) being the most frequently viewed. A total of 24 patients (16.3%, 24/147 ) raised 45 questions using the doctor-patient dialogue module, with the highest proportion related to consultation issues and complications, each accounting for 22.2% (10/45). Twenty-three patients completed the 3-month follow-up, with 12 in the patient education group and 11 in the control group. The patient education group scored higher than the control group in terms of completeness of information acquisition [(4.58±0.51) points vs. (3.91±0.70) points, t=-2.65, P=0.015], while scoring lower in breast symmetry [(3.92±0.79) points vs. (4.63±0.67) points, t=2.33, P=0.030]. There was no significant difference between the two groups in terms of expected breast reconstruction outcome, expected surgical type, and breast softness scores ( P>0.05 for all). Conclusion:The Care Plan platform for whole course management and follow-up of breast reconstruction can assist medical staff in formulating patient-centered management plans, improve patients’ understanding of surgical information, and aid patients in making decisions regarding breast reconstruction methods.

Objective Evaluate the performance of the encephalon state index(ESI)in depth of anesthesia monitoring during clinical surgery,compared with the bispectral index(BIS).Methods ESI and BIS data were collected from 60 patients in a single-center clinical trial to compare their efficacy in measuring the depth of anesthesia.Results Consistency analysis revealed mean differences and standard deviations of-0.18±5.42 and-0.11±6.51 between ESI and BIS for awake and anesthetized states,respectively.Correlation analysis showed a correlation coefficient of 0.92 throughout the operative period.Prediction probability analysis indicated that both ESI and BIS had prediction probabilities of 0.97,effectively predicting anesthesia status.Conclusion ESI and BIS show good equivalence in monitoring depth of anesthesia during clinical surgery,which meet the requirements of clinical anesthesia.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.