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.

Inflammatory breast cancer(IBC)is a rare but highly aggressive subtype of breast cancer characterized by rapid clinical progression and poor prognosis.Although it accounts for only 2%-4%of all breast cancer cases,it is responsible for 8%-10%of breast cancer-related mortality.The etiology of IBC is multifactorial,involving genetic,hormonal,environmental,and socioeconomic factors.Pathologically,IBC is marked by the presence of dermal lymphatic tumor emboli,and molecular subtypes are predominantly HER2-positive and triple-negative,indicating high tumor invasiveness.Diagnosis relies on characteristic clinical manifestations and histopathological confirmation,while imaging techniques such as MRI and PET/CT play important roles in evaluating disease extent and metastasis.Given that IBC is often diagnosed at a locally advanced or metastatic stage,there is currently no specific treatment protocol.Instead,management generally follows the treatment paradigm of non-IBC,emphasizing systemic therapy within a multidisciplinary framework.HER2-positive IBC benefits from chemotherapy combined with dual-targeted anti-HER2 therapy;triple-negative IBC may respond to immune checkpoint inhibitors;and CDK4/6 inhibitors show potential efficacy in hormone receptor-positive subtypes.Despite advancements,the prognosis remains poor,with a high risk of early recurrence and distant metastasis.Prognostic factors include lymph node involvement,molecular subtype,and response to neoadjuvant therapy.As research into the tumor microenvironment and molecular mechanisms deepens,targeted and individualized therapies hold promise for improving outcomes.This review summarizes the epidemiology,pathology,diagnostic criteria,treatment strategies,and prognostic factors of IBC,aiming to inform clinical practice and future research.

Objective:To explore the factors influencing the success rate of culturing patient-derived gastric and colorectal cancer organoids.Methods:From Feb 2022 to Oct 2023, 398 tumor tissue specimens from patients who underwent gastric cancer and colorectal cancer resection at the Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, were used for organoid culture. The clinicopathological factors affecting the success rate of organoid culture were analyzed.Results:The overall success rate of organoid culture in this group was 75.1% (299/398), with the success rate of gastric cancer organoid culture being 79.8%(154/193) and that of colorectal cancer being 70.7% (145/205). Different clinicopathological T stage ( χ2=4.765, P<0.05),histological type ( χ2=11.248, P<0.05), and tumor regression grade (TRG) grade after neoadjuvant chemotherapy ( χ2=7.797, P<0.05) were related to the success rate of organoid culture . Multivariate analysis showed that the TRG grade was an independent influencing factor( P=0.040). For colorectal cancer, different pathological T stage ( χ2=5.108, P<0.05), histological type ( χ2=11.270, P<0.05), and TRG grade after neoadjuvant chemotherapy ( χ2=6.797, P<0.05) were related to the success rate of organoidculture . Different from gastric cancer, the results of multivariate analysis of colorectal cancer showed that the histological type was an independent influencing factor ( P=0.018). Conclusions:The pathologic T stage, histological type of tumors, and TRG of cancer patients all have a significant impact on the success rate of establishing tumor organoids. Among them, the TRG grade is an independent influencing factor for the culture of gastric cancer organoids, and the histological type is an independent influencing factor for colorectal cancer organoids.

Objective:To compare the effects of robotic and laparoscopic radical gastrectomy on short-term clinical outcomes and long-term prognosis in obese patients with gastric cancer.Methods:Clinical data from 231 obese gastric cancer patients undergoing laparoscopic or robotic radical gastrectomy at the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University between Jan 2015 and Dec 2022 was analyzed. After propensity score matching, the patients were divided into robotic surgery group ( n=79) and laparoscopic surgery group ( n=79). The short-term clinical outcomes and long-term prognosis were compared. Results:Compared with the laparoscopic group, the robotic group had a significantly greater number of dissected lymph nodes [(32±13) vs. (26±11), t=2.797, P=0.006], shorter operation time [(245±65) min vs. (272±62) min, t=-2.669, P=0.008], less intraoperative blood loss[(84±69) vs. (119±56) ml, t=-3.502, P=0.001], shorter postoperative hospital stay [(8.2±3.5) vs. (9.6±4.2) d, t=-2.363, P=0.019], and higher hospitalization cost [(102,139±18,303) vs. (77,857±18,325) yuan, t=8.333, P<0.001]. The 5-year overall survival and disease-free survival rates were comparable between the robotic and laparoscopic groups (77.2% vs. 74.7%, P=0.684; and 73.4% vs. 68.4%, P=0.491, respectively). Conclusions:Robotic radical gastrectomy is a safe and feasible alternative for obese gastric cancer patients in experienced hands. It offers advantages in short-term clinical outcomes, however, it fails to provide a significant long-term survival benefit.

Objective:To compare the short- and long-term outcomes of robotic versus laparoscopic gastrectomy in patients with locally advanced gastric cancer after neoadjuvant chemotherapy.Methods:Data from 321 patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy followed by robotic ( n=109) and laparoscopic ( n=212) radical gastrectomy at our center between May 2017 and Sep 2022 was collected. After 1∶1 propensity score matching, 106 patients from each group were included in the final analysis to compare short-term clinical outcomes and long-term prognostic indicators. Results:The robotic group had a significantly lower overall complication rate (13.2% vs. 28.3%, χ2=6.453, P=0.007) and surgery-related complication rate (8.5% vs. 17.9%, χ2=3.333, P=0.043) than the laparoscopic group. The robotic group also retrieved more total lymph nodes (35.3±4.9 vs. 31.4±6.3, t=4.863, P<0.001) and supra-pancreatic lymph nodes (13.1±3.4 vs. 10.1±2.1, t=5.258, P<0.001). Additionally, the robotic group had a shorter operative time [(218±47) min vs. (267±71) min, t=-6.001, P<0.001], less intraoperative blood loss [(47±12) ml vs. (71±17) ml, t=-5.424, P<0.001], and faster postoperative recovery. The 3-year recurrence-free survival rate was significantly higher in the robotic group compared to the laparoscopic group (75.5% vs. 62.3%, P=0.017). Conclusion:Compared with laparoscopic gastrectomy, robotic gastrectomy allows for a more lymph nodes harvest, significantly reduces intraoperative blood loss and complication rates and significantly improves recurrence-free survival.

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.

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*

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.