Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

The current focus of materials science and biomedical science research lies in two-dimensional(2D)MXenes materials,which possess an array of distinctive material attributes.These include superior optical characteristics,a high specific surface area,remarkable hydrophilicity,facile surface functionalization modification and impressive electrochemical properties.These features endow MXenes with vast application potential across multiple domains,particularly in the biomedical realm where advancements in tumor diagnosis and therapy have garnered significant research interest.These advancements primarily center on the enhancement of imaging technology and treatment methodologies.Notably,MXenes exhibit an array of unique physical and chemical properties,including remarkable fluorescence quenching capabilities,superior X-ray attenuation performance and highly efficient photothermal conversion.In the realm of diagnostic technologies,MXenes materials have emerged as a promising candidate for multimodal imaging,encompassing fluorescence imaging,photoacoustic imaging,computed tomography and magnetic resonance imaging(MRI).These materials,through their composite design,offer the potential to transcend the limitations of single-mode diagnostic techniques,thereby fostering innovative approaches in tumor imaging.Furthermore,MXenes exhibit exceptional characteristics as combination therapy materials,particularly in targeted drug delivery and optical therapy for tumor treatment.By harnessing the diverse physical and chemical properties of MXenes,personalized treatment strategies can be realized through precise drug delivery,thereby mitigating the toxic side effects associated with systemic chemotherapy.Currently,a pressing challenge in cancer research lies in the rational design and modification of MXenes probes that possess both diagnostic and therapeutic capabilities.This article aimed to provide a comprehensive review of the latest advancements,opportunities and challenges associated with two-dimensional MXenes materials and their derivatives in the context of tumor diagnosis and treatment.Additionally,it delved into the material synthesis,surface modification and tumor imaging research conducted in this field.Furthermore,it examined the obstacles and limitations encountered in the utilization of MXenes in the present context.The research and development of MXenes materials were integral to nanotherapy,and their novel properties,biological effects and oncological application value were thoroughly analyzed,in order to offer more effective and safer therapeutic options for cancer patients.

Objective To mine temozolomide-related adverse drug event(ADE)signals in the real world and to provide a reference for the safe clinical use of temozolomide.Methods The U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)was used to collect the ADE reporting data of temozolomide in the FAERS database from January 1,2004 to December 31,2022.The signal mining was performed using the report ratio method and Bayesian confidence interval progressive neural network method to analyze the occurrence of ADE.Results In the database,there were 24 725 ADE reports with temozolomide as the primary suspected drug,and a total of 300 ADE signals were identified,involving 23 system organ categories,and the top 5 were blood and lymphatic system diseases,systemic diseases and various reactions of administration sites,various examinations,various neurological diseases,various injuries,poisoning and procedural complications etc.the most frequently reported ADE signals included thrombocytopenia,low platelet count,neutral granulocytopenia,pancytopenia,convulsive attacks,and febrile neutropenia.42 new suspected adverse reactions were discovered,which were not recorded in the instructions,such as pseudomonas skin infection,herpetic meningoencephalitis,hypoglossal nerve paralysis,porokeratosis,etc.Conclusion The common adverse reactions of temozolomide in the real world are generally consistent with the instructions,but some new suspicious adverse reactions have been discovered.During clinical drug use,special attention should be paid to these new adverse reactions,and it is recommended to monitor patients'adverse reactions and take appropriate measures in a timely manner.

【Objective】 To explore the clinicopathological characteristics and comprehensive treatment strategies of prostate mucosa adenocarcinoma under multidisciplinary diagnosis and treatment (MDT) mode. 【Methods】 Data of two patients with typical prostate mucosa adenocarcinoma treated in our hospital during Sep.2020 and Apr.2023 were retrospectively analyzed. 【Results】 In case 1, the clinical manifestation was macroscopic hematuria; multiparametric magnetic resonance imaging (mpMRI) indicated solid prostatic nodules, clinical stage T4N1Mx; initial prostate specific antigen (PSA) was 1.2 ng/mL; ⁶⁸68Ga-prostate specific membrane antigen PET/CT (⁶⁸Ga-PSMA PET/CT) suggested abnormal uptake of nuclear lesions in the prostate (SUV4.2-5.3); biopsy results indicated invasive mucinous adenocarcinoma.After prostate and pelvic field radiotherapy + androgen deprivation therapy (ADT) + antihypertensive treatment, lesions were significantly reduced, and hematuria symptoms were relieved.In case 2, the clinical manifestation was dysuria; initial PSA was 91.78 ng/mL; mpMRI suggested invasion of prostate mass into the bladder and clinical stage of T4N1M1b; ⁶⁸Ga-PSMA PET/CT indicated prostate and pelvic lymph nodes, and multiple bone lesions showed increased nuclide uptake; biopsy results indicated prostate adenocarcinoma with mucinous adenocarcinoma.Initial endocrine treatment was performed.After 3 months, PSA was reduced to 0.083 ng/mL, and imaging showed the tumor was significantly reduced.Robotic-assisted laparoscopic tumor prostatectomy with extended pelvic lymph node dissection was performed, and endocrine adjuvant therapy was continued after surgery. 【Conclusion】 Prostate mucosa adenocarcinoma has different clinicopathological characteristics and prognosis from conventional acinar adenocarcinoma, and the whole-process management under MDT mode is of great value in the diagnosis and treatment of this disease.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Objective:To explore the clinical value of introducing 68Ga PSMA PET / CT into the prostate cancer(PCa)screening clinic, and to analyze the incidence rate and biopsy of PCa in the screening clinic of our hospital. Methods:The data of the people who participated in PCa screening in the urology screening clinic of our hospital from March 2021 to November 2021 were retrospectively analyzed. Serum PSA was used as the screening index. The subjects with PSA≥4ng/ml were first examined by mpMRI to find suspicious nodules, and the positive ones were further examined by 68Ga-PSMA PET/CT to determine the lesions.The puncture target was outlined, and systematic+ targeted puncture was conducted under ultrasound guidance. The age, PSA distribution, puncture detection rate, Gleason score and clinical stage of patients with PCa were recorded. Results:A total of 1 079 subjects were included in the screening, with an average age of (63.9±9.9)(ranging 40-92) years old, and 249 patients (23.1%, 249/1 079) with PSA≥4ng/ml. Among them, 87 cases (87/249, 34.9%) received mpMRI, and 34 cases (34/249, 13.7%) had PI-RADS score ≥3 points. These 34 patients with suspected nodules on MRI were further scanned with 68Ga-PSMA PET/CT, and 11 cases (11/249, 4.4%) had abnormal uptake of PSMA nuclide. A total of 32 patients (12 patients with PSA abnormalities and 20 patients with positive imaging) finally received prostate biopsy, and 11 patients were diagnosed with PCa, with a positive detection rate of 34.4% (11/32), accounting for 1.0% (11/1 079) of the screening population. Among them, 20 patients with positive imaging (9 patients with only mpMRI positive and 11 patients with both mpMRI and 68Ga-PSMA PET/CT positive) underwent system + targeted fusion biopsy, and the positive rate was 45% (9/20). 12 patients (only PSA abnormal) underwent routine systematic puncture biopsy, and the positive detection rate was 16.7% (2/12). The difference between the two groups was statistically significant ( P<0.05). Among the patients with confirmed PCa, 27.3% (3/11) had Gleason score less than 7, and 72.7% (8/11) had Gleason score≥7. Localized PCa (≤T 2) accounted for 45.4% (5/11), local progression (T 3-T 4) accounted for 18.2% (2/11), and metastatic PCa suggested by 68Ga-PSMA PET/CT accounted for 36.4% (4/11), including 3 systemic multiple bone metastases and one bone metastasis with distant lymph node metastasis. Clinically significant PCa accounted for 90.9% (10/11) of the confirmed patients, and the proportion of high-risk patients in localized or locally advanced PCa was 71.4% (5/7). Conclusions:In PCa screening, if 68Ga-PSMA PET/CT is introduced on the basis of conventional mpMRI, the detection rate of clinically meaningful PCa can be improved. Combined with targeted puncture, tumor lesions can be found early and the screening efficiency of PCa can be improved. In this study, the detection rate of PCa in outpatient screening reached 1.0%. In confirmed cases, the proportion of high-risk patients and metastatic patients was higher.

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Objective To understand the situation of cancer screening of community residents and its association with the knowledge of cancer core knowledge, and to provide reference for the formulation of secondary cancer prevention measures. Methods A cross-sectional survey was conducted among 2 037 residents aged 18-79 who lived in Bao 'an District, Shenzhen. Multivariate Logistic regression analysis was used to investigate the relationship between core knowledge and cancer screening behavior after adjusting for age, gender, education, marriage, occupation and smoking. Results The cancer screening rate of community residents was 28.10%, and the screening rate of middle-aged and elderly people aged 40-79 was 33.50 %.The proportion of ^“not very well understanding^”, ^“partial understanding^” and ^“basic understanding^” of the core knowledge of cancer were 43.91%, 42.33% and 13.76%, respectively, which was higher than that of the non-participants. Multivariate analysis showed that the women, the higher the level of education of college/university or above and the higher the level of knowledge of cancer prevention core knowledge, the higher the probability of participating in cancer screening was OR (95%CI ) : 2.40 (1.86-3.12), 1.65 (1.29-2.10), 1.38 (1.18 - 1.62), respectively. Conclusion The proportion of cancer screening in community residents needs to be improved, and the degree of core knowledge of cancer is closely related to cancer screening behavior. It is suggested to increase the publicity and education of the core knowledge of cancer, and at the same time, carry out the health education of secondary cancer prevention for the key population such as men and people with low education level, so as to improve the proportion of ^“early detection, early diagnosis and early treatment^” of cancer.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic