ObjectiveTo investigate the spontaneous premature cardiac aging in SHJH^hr mice. MethodsA comparative study was conducted between SHJH^hr mice (SHJH^hr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJH^hr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJH^hr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJH^hr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJH^hr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJH^hr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Objective To investigate the risk factors for postoperative gastrointestinal bleeding (GIB) in patients with type A aortic dissection, and further discuss its prevention and treatment. Methods The clinical data of patients with type A aortic dissection admitted to the Department of Cardiovascular Surgery of the First Affiliated Hospital of Naval Medical University from 2017 to 2021 were retrospectively analyzed. Patients were divided into a GIB group and a non-GIB group based on the presence of GIB after surgery. The variables with statistical differences between two groups in univariate analysis were included into a multivariate logistic regression model to analyze the risk factors for postoperative GIB in patients with type A aortic dissection. Results There were 18 patients in the GIB group including 12 males and 6 females, aged 60.11±10.63 years, while 511 patients in the non-GIB group including 384 males and 127 females, aged 49.81±12.88 years. In the univariate analysis, there were statistical differences in age, preoperative percutaneous arterial oxygen saturation (SpO2)<95%, intraoperative circulatory arrest time, postoperative low cardiac output syndrome, ventilator withdrawal time>72 hours, postoperative FiO2≥50%, continuous renal replacement therapy (CRRT) rate, extracorporeal membrane oxygenation (ECMO) rate, infection rate, length of hospital stay and ICU stay, and in-hospital mortality (all P<0.05). In the multivariate logistic regression analysis, preoperative SpO2<95% (OR=10.845, 95%CI 2.038-57.703), ventilator withdrawal time>72 hours (OR=0.004, 95%CI 0.001-0.016), CRRT (OR=6.822, 95%CI 1.778-26.171) were risk factors for postoperative GIB in patients (P≤0.005). In the intra-group analysis of GIB, non-occlusive mesenteric ischemia (NOMI) accounted for 38.9% (7/18) and was the main disease type for postoperative GIB in patients with type A aortic dissection. Conclusion In addition to patients with entrapment involving the superior mesenteric artery who are prone to postoperative GIB, preoperative SpO2<95%, ventilator withdrawal time>72 hours, and CRRT are independent risk factors for postoperative GIB in patients with type A aortic dissection. NOMI is a major disease category for GIB, and timely diagnosis and aggressive treatment are effective ways to reduce mortality. Awareness of its risk factors and treatment are also ways to reduce its incidence.

As an important advance in the treatment of anti-tumor therapy,immune checkpoint inhibitors significantly prolong the survival of patients with malignant tumors.At the same time,immune-related adverse reactions are also increasing,among which ICIs have increased the risk of acute coronary events,but clinical reports are rare.This paper analyzes the history of a patient with pulmonary small cell neuroendocrine carcinoma who developed acute myocardial infarction after ICIs treatment,suggesting that clinicians should be alert to the occurrence of ICIs-related acute myocardial infarction,and improve the prognosis of patients through early identification and intervention.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective To observe18F-FDG PET/MRI manifestations of gray matter heterotopia(GMH)related epilepsy.Methods Data of 27 patients with GMH and epilepsy diagnosed with MRI were retrospectively analyzed.Brain 18 F-FDG PET/MRI manifestations and complicated brain malformations were observed,and the classification of GMH were performed.Results Among 27 cases,periventricular GMH,focal subcortical GMH,subcortical lamellar(band)GMH and mixed GMH were detected each in 15,2,2 and 8 cases,respectively.Compared with cerebral white matter around the lesion or in the contralateral mirror area of the lesion,glucose hypermetabolism and glucose hypometabolism were found in 22 and 3 cases,respectively,while glucose metabolism was normal in 2 cases.Compared with gray matter in precentral gyrus,glucose hypermetabolism and glucose hypometabolism were observed in 8 and 16 cases,respectively,while glucose metabolism was normal in 3 cases.Six cases complicated with cerebral fissure deformity,6 cases with bilateral cerebellar hemispheric volume reduction,1 case with absence of pellucid septum and lower fornix,1 case with dysplasia of corpus callosum and 1 case with polymicrogyria.Conclusion 18 F-FDG PET/MRI manifestations of GMH related epilepsy had certain characteristics,which were helpful for clinical diagnosis.

Objective To prepare Zishen pills as gel plaster according to the prescription,and investigate its transdermal absorption characteristics in vitro.Methods Based on preliminary experiments,the matrix prescription of the gel plaster was optimized by single-factor tests and the Box-Behnken design.Evaluation indicators included initial viscosity,viscosity retention and sensory scores.The modified Franz diffusion cell was used to investigate the effect of penetration enhancers on the transdermal characteristics of gel plaster in vitro,with the permeability of neomangiferin,phellodendrine hydrochloride,mangiferin and berberine hydrochloride as evaluation indicators.Results The prescription dosage of the preferred matrix for the Zishen gel plaster was sodium polyacrylate NP700 2.55 g,glycerin 11.04 g,polyvinylpyrrolidone K90 1.13 g,tartaric acid 0.1 g,glycyrrhizin 0.1 g,kaolin 0.3 g,and distilled water 15 g.Among different types and concentrations of permeation enhancers,5%aminoketone showed the best permeation performance.The permeation rates for neomangiferin,phellodendrine hydrochloride,mangiferin,and berberine hydrochloride were 1.5338,1.7809,2.3247 and 20.0899 μg·(cm2)-1·h-1,and the penetration rates were 2.4319,1.9408,1.9604 and 1.4701,respectively.The percutaneous absorption curve of the drug conformed to the zero-order kinetic equation.Conclusion The preparation process of the obtained gel plaste is stable and feasible,with good adhesive properties,sustained drug release,and favorable in vitro percutaneous permeability,indicating potential clinical application value.