Objective:To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease.Methods:For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis.Results:Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient′s serum levels of adrenocorticotropic hormone and cortisol returned to normal.Conclusions:Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

Objective:To investigate the relationship between bone mineral density (BMD) and metabolic syndrome (MS) and its components in men.Methods:The cross-sectional study method was used. The subjects were male physical examination population who were examined in the Health Examination Center of the Affiliated Hospital of Hebei University from January 2021 to December 2021. According to the MS diagnostic criteria, they were divided into MS and non MS groups. The BMD of femur was measured by dual energy X-ray bone density analyzer. The prevalence rate and bone mineral density of osteopenia, osteoporosis, metabolic syndrome in different age groups, and the differences of metabolic indicators between MS and non MS groups and the impact of MS on BMD were analyzed. Multivariate linear stepwise regression was used to analyze the risk factors of male bone mineral density.Results:6 191 subjects were included in the study. The prevalence of osteoporosis (OP) was 9.50%(588/6 191) and the prevalence of MS was 31.64%(1959/6 191) in healthy men. The prevalence of age, body mass index (BMI), fasting plasma glucose (FPG), total glyceride (TG), total cholesterol (TC), uric acid, diastolic blood pressure, systolic blood pressure and fatty liver in MS group were higher than those in non-MS group, with statistically significant difference (all P<0.05). The high density lipoprotein cholesterol (HDL-C) in MS group was lower than that in non-MS group, with statistically significant difference (all P<0.05). There were no significant difference in the prevalence of OP and BMD between the MS group and the non-MS group (all P>0.05). There was no statistically significant difference in BMD values among different MS groups, but after adjusting BMI, when the MS group score increased from 0 to 4, the BMD value decreased gradually, and the difference was statistically significant ( P<0.05). Multiple linear regression analysis showed that BMD was positively correlated with BMI and diastolic blood pressure, but negatively correlated with age, systolic blood pressure and prevalence of fatty liver disease (all P<0.05). Conclusions:With the increase of the number of MS components, BMD in men decreased gradually. BMD in men was positively correlated with BMI and diastolic blood pressure, but negatively correlated with age, systolic blood pressure and prevalence of fatty liver disease.

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading I-labeled hollow copper sulfide nanoparticles and paclitaxel (I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. F-fluordeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (<0.05) following intra-tumoral (i.t.) injection with I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.