ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective To explore the efficacy of hypofractionated radiotherapy at different time intervals after surgery for keloid,and to analyze the factors affecting the efficacy.Methods A total of 76 patients who underwent 20 Gy/5 postoperative radiotherapy regimen in the Fifth Affiliated Hospital of Zhengzhou University from January 2021 to June 2023 were selected as study subjects,and a total of 100 keloids were divided into effective group(n=79)and recurrence group(n=21).Regular follow-up and record of the patients after radiotherapy treatment effect and adverse effects,and multivariate Logistic was used to analyze factors of recurrence in keloid patients.Results Multivariate Logistic regression analysis found that postoperative radiotherapy time and scar incision length were related to recurrence after treatment,radiotherapy within 7h of surgery was an independent risk factor for recurrence after treatment(OR＞1,P=0.022),and scar incision≤5cm was an independent protective factor for recurrence after treatment(OR＜1,P=0.028).Conclusion Surgical excision combined with hypofractionated radiotherapy is one of the effective measures to prevent and treat keloid recurrence,though keloids on the trunk may need more effective treatment options.The recurrence rate of radiotherapy initiated 7-48h after surgery is relatively the lowest,and it is worthy of clinical promotion and application.

Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.

Alzheimer′s disease is a serious neurodegenerative disorder. Approximately 80% to 90% of patients are accompanied by behavioral and psychological symptoms of dementia (BPSD), which manifest as a series of behavioral, psychological and mental abnormalities. These abnormalities can accelerate the cognitive deterioration and premature death of patients, and thus are regarded as important clinical symptoms. However, the pathogenesis of BPSD is still unknown, and treatment methods are limited. The pathogenesis of BPSD from the perspective of neuroimaging and pathophysiology, and possible treatment measures were analyzed in this article, in order to provide references for the early diagnosis and treatment of BPSD.

Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

To investigate the effect of capsaicin(CAP)on the replication of bovine viral diarrhea vi-rus(BVDV).Bovine nasal turbinate osteoblasts(BT)infected with BVDV served as the research model,and viral gene and protein levels were evaluated using RT-qPCR and Western blot.Moreo-ver,molecular docking,molecular dynamics simulation,and oil red O staining were applied to ana-lyze the mechanism by which CAP inhibits BVDV replication.The results revealed no significant effect of CAP at 6.25,12.5,25,and 50 mg/L on the viability of BT cells.CAP was found to signifi-cantly inhibit BVDV 5′UTR RNA and E2 protein levels,according to the antiviral effect study.Molecular docking and molecular dynamics simulations indicated that CAP could bind with high affinity to the active site of PI3K.Additional mechanistic studies indicated that CAP significantly reduced the activation of the PI3K/AKT signaling pathway triggered by BVDV.Furthermore,CAP notably decreased the mRNA levels of FASN,SREBP-1,and ACC-1,which are crucial fatty acid synthesis enzymes in the downstream PI3K/AKT signaling pathway,as well as the levels of lipid droplets.Interestingly,the addition of exogenous oleic acid greatly diminished the antiviral effec-tiveness of CAP and significantly lowered the mRNA levels of IFN-α and IFN-β.The results reveal for the first time that CAP can inhibit BVDV replication,establishing a foundation for its preven-tion and the development of feed additives.