Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Prehypertension/diagnosis* ; Risk Factors ; Hypertension ; Incidence

Objective To analyze the composition and change of the disease spectrum of inpatients in a third-level women's and Children's Hospital in Foshan City,so as to provide evidence for the prevention and treatment of common diseases among local women and children and promote the development of maternal and child health work.Methods The primary diagno-sis and other medical data of home page of inpatients from 2013 to 2022 were collected and classified according to the Internation-al Classification of Diseases(ICD-10),and the changes of age,gender and disease spectrum of hospitalized patients in different discharge year groups were compared.Results The average increase rate of patients discharged from hospital in 2022 compared with 2013 is 9%.The majority of discharged patients were female adults,accounting for 65.2%.Adult female patients are mainly hospitalized for pregnancy,childbirth and puerperium,neoplasms,and genitourinary diseases,the composition of gynecological neoplasms and genitourinary diseases increased.Most of the hospitalized children were boys,with a sex ratio of 1.9 ∶1.Respirato-rydiseases and some conditions originating in the perinatal period in the decade from 2013 to 2022 were in the top two of the dis-ease spectrum of pediatric patients,and the ranking of Symptoms,signs and anomal clinical and laboratory findings,not else-where classified and neurological diseases increased rapidly.Conclusion Pregnancy,childbirth,puerperal and other special fe-male health conditions are still the main reasons for female hospitalization.It is necessary to continue to guarantee medical re-sources and strengthen the diagnosis and treatment ability of female tumor.Children's respiratory diseases and certain conditions originating in the perinatal period are still disciplines that need to be focused,while children's neurological diseases also need to continue to focus on due to their rapid growth.

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/therapeutic use* ; Humans ; Reproducibility of Results ; Rodentia

OBJECTIVETo investigate the effect of intensive rosuvastatin therapy on adhesion molecules in patients with peripheral atherosclerosis and explore the possible upstream mechanism.

METHODSTwenty asymptomatic patients with peripheral atherosclerosis were enrolled and given 5-20 mg/day rosuvastatin for 3 months. Before and after the treatment, the lipid profile and plasma vascular cell adhesion molecule-1 (VCAM-1) levels were examined. The expression of intercellular adhesion molecule-1 (ICAM-1) in the mononuclear cells was measured using flow cytometry, and the mRNA and protein expressions of peroxisome proliferator-activated receptor γ (PPARγ) were detected using RT-PCR and Western blotting, respectively.

RESULTSCompared with the baseline levels, ICAM-1 expression decreased and PPARγ protein expression increased in the lymphocytes. Rosuvastatin therapy did not produce obvious effects on plasma VCAM-1 level or ICAM-1 expression in the monocytes in these patients.

CONCLUSIONRosuvastatin produces anti-inflammatory effects by decreasing the expression of ICAM-1 in mononuclear cells, and its upstream mechanism may involve the PPARγ pathway.

Atherosclerosis ; drug therapy ; metabolism ; Cell Adhesion Molecules ; metabolism ; Female ; Fluorobenzenes ; administration & dosage ; therapeutic use ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Middle Aged ; Monocytes ; drug effects ; metabolism ; PPAR gamma ; metabolism ; Pyrimidines ; administration & dosage ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; administration & dosage ; therapeutic use ; Vascular Cell Adhesion Molecule-1 ; metabolism

OBJECTIVETo study the chemical constituents of Phlomis umbrosa.

METHODChemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and preparative HPLC). The structures were elucidated on the basis of spectral data analysis.

RESULTThirteen compounds were identified as oleanolic acid (1), corosolic acid (2), hederagenin (3), arjunolic acid (4), belleric acid (5), 3beta-hydroxy-29-al-12-en-28-oleanoic acid (6), butyrospermol (7), beta-sitosterol (8), daucosterol (9), caffeic acid (10), vanillic acid (11), p-hydroxy-benzoic acid (12), 3, 4-dihydroxy-benzoic acid (13).

CONCLUSIONCompounds 3 9, 11-13 were isolated from the plant for the first time.

Organic Chemicals ; analysis ; chemistry ; isolation & purification ; Phlomis ; chemistry ; Plant Roots ; chemistry