BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

Objective:To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors.Methods:Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed.Results:Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing′s syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas.Conclusions:Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

Objective:To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty.Methods:Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty.Results:A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR=0.743, 95% CI: 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR=0.509, 95% CI: 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions:Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

Objective:To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai.Methods:Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength.Results:A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR=1.41, 95% CI: 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR=1.67, 95% CI: 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR=1.30, 95% CI: 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR=1.57, 95% CI: 1.05-2.35; OR=2.40, 95% CI: 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P>0.05). Conclusions:This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

Objective To evaluate 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging in clinical diag-nostic of pheochromocytoma and paraganglioma(PPGL).Methods This was a retrospective study.359 PPGL pa-tients diagnosed by pathology microscopy were included.The diagnostic sensitivity and influencing factors on 99mTc-HYNIC-TOC somatostatin receptor and 131 I-MIBG imaging were analyzed.Results The positive rate of 99mTc-HYN-IC-TOC somatostatin receptor scintigraphy was 57.7%(184/319)and 131I-MIBG imaging was 83.2%(232/279).The positive rates of 99m Tc-HYNIC-TOC somatostatin receptor imaging in the adrenal glands,retroperitoneum,head and neck,heart and mediastinum,pelvis and bladder were 53.3%,62.5%,95.0%,66.7%,50.0%and 11.0%respec-tively and the positive rates of 131I-MIBG imaging were 86.7%,88.5%,45.4%,50.0%,75.0%and 33.3%respec-tively.The positive rate of the two imaging did not showed difference among patients with different genetic back-grounds(SDH,VHL,RET mutations).The median maximum diameter of tumors was 4.4(3.0,6.1)cm.and the diag-nostic sensitivity of somatostatin receptor imaging and 131 I-MIBG imaging for larger tumors(≥4.4 cm)was signifi-cantly higher than those for the smaller tumor group(＜4.4 cm)(64.0%vs.51.3%;92.3%vs.74.1%)(P＜0.01).Tumors in 19 patients(5.3%)failed to uptake neither imaging method.Conclusions This is the largest PPGL cohort in China concerning 99m Tc-HYNIC-TOC somatostatin receptor imaging and 131 I-MIBG imaging.The sensitivity of 131 I-MIBG imaging is higher than that of 99m Tc-HYNIC-TOC somatostatin receptor imaging,but for some tumors,such as head and neck paraganglioma,the latter has obvious advantages.These two imagings technol-ogies are complementary and the choice of them should depend the individual situation of patients.

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.

Purpose/Significance To sort out the literature in the field of traditional Chinese medicine(TCM)in China in the past decade,and to expound the hot topics and development trends in this field.Method/Process Literature in the field of TCM in Wanfang Data from 2013 to 2022 is searched.The abstracts are taken as the research objects,the topics are extracted by BERTopic model,and CiteSpace is used for visualization and analysis.Result/Conclusion 12 683 papers in Chinese are included,and the 5 topics are found:clinical trials and efficacy,research on pathogenesis and pharmacology,the development of the field of TCM,treatment of chronic dis-ease,drug analysis and literature research.The paper makes an in-depth analysis of the topic of the development of traditional Chinese medicine,which continues to grow in popularity,and puts forward that the deep integration of artificial intelligence(AI)and TCM is the future trend.

Purpose/Significance The paper discusses the construction of the current elderly health policy system by using policy text min-ing and quantitative evaluation,and provides references for future policy adjustment and optimization.Method/Process Policies on elderly health issued by the relative departments from 2019 to 2023 are analyzed.The ROST text data mining tool is used to extract high-frequency words and build semantic networks.Gephi is utilized to visualize social network relationships for text analysis.Quantitative analysis of these policies is conducted using the PMC index model.Results/Conclusion The high-frequency words such as"national","society","knowl-edge","resources",and"guarantee"are identified as key areas in elderly health policies,which are interconnected within the social network.The overall trend of the elderly health policy formulation is positive.It is suggested to improve the accuracy and adaptability of the policy,clari-fy the time node and core elements of the policy,and enhance the strategic analysis of the function and content of the policy.

Objective To summarize the clinical characteristics of patients with occupational melanosis. Methods Diagnostic data of 69 patients with occupational melanosis was analyzed using retrospective analysis. Results The main occupational hazards for the 69 patients with occupational melanosis were coal tar, petroleum and its fractionated products, pigments and dyes and their intermediates, rubber additives and rubber products. The median length of occupational exposure and disease latency were 8.0 and 6.0 years, respectively, with a highly positive correlation between them (Spearman correlation coefficients=0.962, P<0.01). Skin lesions were mainly found on exposed areas such as the face-to-neck and limbs, prevalence of 94.2% and 75.4% respectively. And 78.3% of patients had skin lesion on more than two sites. The lesions were mostly in the form of irregular flakes (59.4%), with a gray-black color (44.9%). About 43.5% of patients experienced skin itching. Complete blood count, liver function, and kidney function were all within normal ranges. Skin biopsy results showed that epidermal hyperkeratosis, thinning of the spinous layer, liquefaction degeneration of basal cells, increased superficial dermal melanocytes, and infiltration of lymphocytes, histiocytes, and melanocytes around the blood vessels. Reflectance confocal microscopy (RCM) detection showed focal liquefaction degeneration of basal cells in the lesions, with a significant infiltration of melanocytes and inflammatory cells in the dermal papillae and superficial layers. Conclusion The primary target organ of occupational melanocytes is the skin, and no damage to other organs was identified thus far. Results from skin biopsies and RCM examinations can be used for differential diagnosis.