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.

OBJECTIVE To study the improvement effect and mechanism of Shuhou tongqi formula on intestinal injury in mice with postoperative ileus （POI）. METHODS Mice were randomly divided into sham operation group， model group， positive control group （Mosapride citrate tablets， 1.95 mg/kg）， and Shuhou tongqi formula group （1.88 g/kg）， with 6 mice in each group. Except for the sham operation group， POI model was induced in other groups by typical small intestinal interference. Each group was given relevant drug liquid/water， once a day， for consecutive 2 days. After the last medication， the percentage of carbon powder propulsion in small intestine was detected， and pathomorphological changes in ileum tissue of mice were observed. The serum levels of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， motilin （MTL） and somatostatin （SS） were all detected； the expression levels of Toll-like receptor 4 （TLR4）， nuclear factor κB （NF-κB p65） and p38 mitogen-activated protein kinase （p38 MAPK） were determined in ileal tissue of mice； the gut microbiota of colon contents was analyzed in each group of mice. RESULTS After the intervention of Shuhou tongqi formula， pathological damage such as intestinal wall atrophy and mucosal capillary congestion in ileum tissue were improved significantly； the percentage of carbon powder propulsion and the serum level of IL-10 and MTL were increased significantly （P＜0.05）； however， serum levels of TNF-α， IL-6 and SS， the expressions of TLR4， NF-κB p65 and p38 MAPK were decreased significantly （P＜0.05）. The analysis of gut microbiota showed that Shuhou tongqi formula could significantly increase ACE， Chao1， Shannon and PD indexes， and relative abundance of Akkermansia （P＜0.05）， but decreased relative abundance of Proteobacteria， Ligilactobacillus and Escherichia-Shigella significantly （P＜0.05）. CONCLUSIONS Shuhou tongqi formula can improve intestinal injury and inflammatory reaction of POI mice， the mechanism of which may be associated with inhibiting the activity of TLR4/ NF-κB/MAPK signaling pathway， regulating the levels of gastrointestinal hormones and improving the disturbance of intestinal flora in mice. E-mail：1643589936@qq.com

Objective:To systematically evaluate the clinical efficacy of Ruiyun procedure for hemorrhoids(RPH)combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids compared with MMH alone.Methods:Relevant literature was retrieved from China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their establishment to Jan 2023 using computers.Clinical randomized controlled trials(RCTs)of RPH combined with MMH and MMH alone in the treatment of mixed hemorrhoids were selected and analyzed,and meta-analysis was conducted using RevMan5.3 software.Results:A total of 30 RCTs were included,involving 4 609 patients.Results of Meta-analysis showed that there were statistically significant differences in surgical efficacy(RR=1.05,95% CI:1.02-1.08,P= 0.003),postoperative margin edema(RR=0.36,95% CI:0.27-0.49,P＜0.01),postoperative anal pain(RR=0.35,95% CI:0.23-0.53,P＜0.01),postoperative rectal bleeding(RR=0.35,95% CI:0.17-0.72,P=0.004),postoperative anal stenosis(RR=0.26,95% CI:0.11-0.59,P=0.001)and postoperative urinary retention(RR=0.77,95% CI:0.63-0.93,P=0.007)between RPH combined with MMH group and MMH group.Conclusion:Compared with MMH alone,RPH combined with MMH in the treatment of mixed hemorrhoids can reduce the incidence of postoperative side effects,such as postoperative margin edema,anal pain,rectal bleeding,anal stenosis,and urinary retention,with a relatively higher efficiency.

Objective To investigate the authentic experience in social participation among the patients with enterostomy,and explore the primary obstacles in social participation,so as to provide a basis for targeted guidance and measures for psychological intervention.Methods A method of descriptive phenomenological research was used in this qualitative research.Ten patients discharged from our hospital after enterostomy surgery were enrolled in this study.The participants were interviewed with a semi-structured questionnaire through the method of purpose sampling.The data acquired from the interviews were analysed and summarised by using the Colaizzi seven-step analysis.Themes were classified and extracted by reading,analysing,reflecting,classifying of the acquired data.Results Three themes were extracted with eight dimensions covering(a)psychosocial disorders with the dimensions of stigma,ostomy-related anxiety and concern,(b)low social participation with the dimensions of low social initiative,estrangement of interpersonal relationships,increased economic burden of social interaction,and(c)poor social adaptability with the dimensions of negative coping style,poor operative skills in ostomy care and poor utilisation of information about ostomy.Conclusions Patients with enterostomy usually encounter various difficulties in social participation and are lack of corresponding support.Medical staff should pay attention to the positive psychological guidance over the period of hospitalisation as well as training in operation skills for stoma.Moreover,healthcare workers should provide the patients with high-quality and continuous care after the patients have returned home and increase psychological and social supports,as well as consultations to improve the quality of life of the patients with enterostomy.

Objective:To analyze and summarize clinical and pathological characteristics of clear cell papulosis (CCP) .Methods:Clinical data were collected from 57 children with CCP, who were diagnosed in Department of Dermatology, Children′s Hospital of Chongqing Medical University from November 2014 to March 2022, and their clinical and pathological characteristics were analyzed.Results:Among the 57 patients, 30 were males and 27 were females; their age ranged from 6 months to 7 years and 10 months; the age at onset ranged from 1 to 74 months, and 39 (68.4%) experienced onset of disease in infancy; the course of disease ranged from 1 to 84 months. Skin lesions mainly manifested as millet- to soybean-sized roundish white macules or short bar-like white macules measuring 1 - 2 cm in length. Most patients (49 cases, 85.9%) had skin lesions less than 20 in number. The most common location of skin lesions was the lower abdomen (35 cases, 61.4%), followed in turn by chest or upper abdomen (34 cases, 59.6%), anterior axilla or armpit (17 cases, 29.8%), and vulva (11 cases, 19.3%). Short bar-like white macules predominated on the chest or upper abdomen (23/34, 65.7%) and anterior axilla or armpit (10/17), roundish white macules predominated on the lower abdomen (30/35, 85.7%), and the vulvar lesions all manifested as roundish white macules. Histopathological findings showed that slightly larger cells with abundant clear cytoplasm were scattered in or above the basal layer of the epidermis, and these cells were positive for cytokeratin 7, carcinoembryonic antigen, and periodic acid-Schiff staining.Conclusion:CCP mainly occurred in young children, roundish white macules predominated on the lower abdomen and vulva, and short bar-like white macules predominated on the chest or upper abdomen, as well as on the anterior axilla or armpit, indicating that CCP has strongly identifiable clinical features.

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

【Objective】 To investigate the level of glycosylated hemoglobin (HbA1c) in apheresis platelet donors, so as to further ensure the safety of apheresis platelet donors and provide guidance for the recruitment strategy. 【Methods】 Apheresis platelet donors from July 2018 to December 2020 were selected and venous blood was drawn. The glycosylated hemoglobin detection was conducted for donors who had never did this before or did this 3 months ago, and glycosylated hemoglobin >6.0% was regarded as abnormal. 【Results】 A total of 986 blood donors were detected, among which 32 donors with abnormal glycosylated hemoglobin were found, rated at 3.25%. With the increase of age and BMI(height and body mass index), the proportion of abnormal glycosylated hemoglobin increased, but the 51~60 age group and BMI > 28.0 group were not the highest, which may be related to the source of samples.The rate of abnormal glycosylated hemoglobin was highest in 40~50 years old group (5.43%, 15 / 276) and BMI ranged of 24.0~27.9 (4.04%, 9 / 223), and lowest (0.85%, 1 / 118) in 18~25 years old group and BMI >28.0(none). 【Conclusion】 The abnormal glycosylated hemoglobin is closely related to age and BMI. Therefore, we should give priority to young and underweight donors when recruiting blood donors, which can improve efficiency and maximize the safety of blood donors.

Continuous renal replacement therapy (CRRT) has become an effective multiple organ support therapy instead of single renal replacement as initially expected, and it is widely used in intensive care unit (ICU). After the outbreak of coronavirus disease 2019 (COVID-19), a series of expert recommendation or consensus have been developed to diagnose and treat the disease, including CRRT in acute kidney injury (AKI) and hyper inflammatory response. However, CRRT in COVID-19 is extraordinarily different from regular one due to different pathophysiology and infectious clinical scenarios. Accordingly, the paper aims to elaborate the similarities and differences between CRRT in COVID-19 and routine treatment in terms of safety and accessibility, indications and timing, clinical operation, anticoagulation, fluid management, prevention and control of infectious diseases, etc.

Objective: To analyze clinical features and prognosis of 15 children with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) . Methods: Clinical features, histopathological findings, treatment outcomes in 15 patients, who were diagnosed with HVLPD in the Department of Dermatology, Children′s Hospital of Chongqing Medical University from 2014 to 2018, were retrospectively analyzed. Results: Among the 15 patients, 7 were males and 8 were females. The age of onset ranged from 2 to 13 years, and the average age was 6.5 years. Main clinical manifestations included facial edema, and papules, blisters, ulcers and crusts repeatedly occurring on both the sun-exposed parts such as the face and limbs and non-sun-exposed parts such as the trunk. Of the 15 patients, 13 had intermittent fever, 13 had hepatosplenomegaly, and 15 had lymphadenectasis. Moreover, kidney failure occurred in 1 patient, hemophagocytic syndrome occurred in 2, and lymphoma occurred in 1. Laboratory examination showed that 15 patients were all positive for Epstein-Barr virus (EBV) -immunoglobulin G (IgG) antibody, and all negative for EBV-IgM antibody. Additionally, high replication of EBV DNA was detected. Histopathological study of skin lesions showed mild to dense perivascular and periadnexal infiltration of lymphocytes in the dermis and subcutaneous tissue. Immunohistochemistry study showed positive staining for CD4 and CD8 in 13 of 15 patients, for CD56 in 7 of 15 patients, and for CD3 in 12 of 13 patients. Moreover, 9 of 11 cases were detected positive for T-cell intracellular antigen-1, 8 cases were all detected positive for granzyme B, and the Ki-67 proliferation index ranged from 3% to 50% in 11 of 12 cases. The treatment protocols were similar among the 15 patients. After the treatment, 2 patients showed stable disease condition, and 10 experienced relapse. During the follow-up, 2 patients developed hemophagocytic syndrome, 1 developed lymphoma, and the 3 patients finally died of the worsening condition after chemotherapy. Conclusions HVLPD is closely associated with chronic active EBV infection. Its clinical symptoms can be relieved after immunomodulatory therapies such as glucocorticoids, gamma globulin and interferon, and the clinical manifestations, treatment outcomes and prognosis vary greatly among different patients.

Bone marrow mesenchymal stem cells (BMSCs) and ideal adult stem cells for alveolar bone regeneration considerably help restore the structure and function of the periodontium and promote the healing of periodontal disease. Thus, BMSC features, especially the mechanism of osteogenic differentiation, has recently become a research hotspot. Tumor necrosis factor-α (TNF-α), which is the main factor in the periodontal inflammatory microenvironment, is directly related to the osteogenic differentiation of BMSCs. Exploring the TNF-α-regulated differentiation mechanism of BMSCs aids in the search for new treatment targets. Such investigation also promotes the development of stem cell therapy for periodontal diseases. This article aims to describe the potential of TNF-α in regulating the osteogenic differentiation of stem cells.
Adult ; Adult Stem Cells ; Bone Marrow Cells ; Bone Regeneration ; Cell Differentiation ; Chronic Periodontitis ; Hematopoietic Stem Cells ; Humans ; Osteogenesis ; Periodontal Ligament ; Periodontium ; Stem Cell Transplantation ; Tumor Necrosis Factor-alpha ; Wound Healing