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.

Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

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.

Effective referral management of health and clinical services in maternal and child health hospitals plays an important role in enhancing patients′ medical experience, improving the efficiency and quality of maternal and child health services. A tertiary grade A maternal and child health hospital has carried out a practice of health and clinical service referral management based on information technology construction. A referral information module embedded in the hospital information system has been designed and constructed, and started to be applied in outpatient clinics in July 2021. At the same time, corresponding system and process construction, as well as quality control management and continuous improvement, have been carried out. The outpatient referral rate from July to December 2021 was 2.8% (11 466/412 808), from January to June 2022 it was 5.6% (22 705/402 586), from July to December 2022 it was 5.5% (22 233/402 959), and from January to June 2023 it was 6.7% (23 373/347 898). The referral rate has continued to improve and can provide reference for the referral management of other maternal and child health institutions.

Objective:Development and validation of a nomogram for predicting the 4-year incidence of type-2 diabetes mellitus (T2DM) in a Chinese population was attempted.Methods:This prospective cohort study was conducted in Shijingshan District Pingguoyuan Community (Beijing, China) from December 2011 to April 2012 among adults aged≥40 years not suffering from T2DM. Finally, 8 058 adults free of T2DM were included with a median duration of follow-up of 4 years. Participants were divided into a modeling group and verification group using simple random sampling at a ratio of 7∶3. Univariate and multivariate Cox proportional risk models were applied to identify the independent risk predictors in the modeling group. A nomogram was constructed to predict the 4-year incidence of T2DM based on the results of multivariate analysis. The Concordance Index and calibration plots were used to evaluate the differentiation and calibration of the nomogram in both groups.Results:A total of 5 641 individuals were in the modeling group and 2 417 people were in the validation group, of which 265 and 106 had T2DM, respectively, at 4-year follow-up. In the modeling group, age ( HR=1.349, 95% CI 1.011-1.800), body mass index ( HR=1.347, 95% CI 1.038-1.746), hyperlipidemia ( HR=1.504, 95% CI 1.133-1.996), fasting blood glucose ( HR=4.189, 95% CI 3.010-5.830), 2-h blood glucose level according to the oral glucose tolerance test ( HR=3.005, 95% CI 2.129-4.241), level of glycosylated hemoglobin ( HR=3.162, 95% CI 2.283-4.380), and level of γ-glutamyl transferase ( HR=1.920, 95% CI 1.385-2.661) were independent risk factors for T2DM. Validation of the nomogram revealed the Concordance Index of the modeling group and validation group to be 0.906 (95% CI 0.888-0.925) and 0.844 (95% CI 0.796-0.892), respectively. Calibration plots showed good calibration in both groups. Conclusion:These data suggest that our nomogram could be a simple and reliable tool for predicting the 4-year risk of developing T2DM in a high-risk Chinese population.

Objective:To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population.Method:This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups.Results:A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio ( HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95% CI 1.19-1.98), 1.60 (95% CI 1.23-2.10), and 1.57 (95% CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group ( P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level ( P<0.001). Conclusions:A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.

Objective:To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas.Methods:This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas.Results:The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [ M ( Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas ( n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) ( r=-0.11, P<0.001), growth hormone ( r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas ( n=297) was positively correlated with growth hormone ( r=0.46, P<0.001), but negatively correlated with male testosterone ( r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas ( n=155) was positively correlated with the ACTH level at 8∶00 AM ( r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM ( P>0.05). The tumor size of prolactinomas ( n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions:The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

A 38-year-old female presented with irregular menstruation and hirsutism that started at age of 16 and diagnosed with polycystic ovary syndrome at age of 29 with elevated testosterone. When treated with ethinestradiol cyproterone tablets, her menstruation returned to normal and androgen levels was not changed. At age of 38 she was referred to the hospital with infertility, a diagnosis of nonclassical 21-hydroxylase deficiency was confirmed using 17-hydroxyprogesterone, dehydroepiandrosterone-sulfate, a cosyntropin-stimulation test and genetic test. This case suggested that nonclassical congenital adrenal hyperplasia should be considered when a patient is presented with oligomenorrhea, hirsutism with hyperandrogenemia and infertility.

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

Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.