Establishment and evaluation of a CT-based radiomic model for AIDS-associated pulmonary cryptococcosis.

BACKGROUND: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model. METHODS: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model. RESULTS: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists. CONCLUSIONS: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.

[Effect of Social Support on Multimorbidity and Related Outcomes of Middle-Aged and Older Adults in China].

Objective: To analyze the current status of social support for middle-aged and older adults with multimorbidity and to explore the correlation between different dimensions of social support and multimorbidity and the related outcomes on the basis of China Health and Retirement Longitudinal Study (CHARLS) 2015 survey data so as to reveal the complex social background of multimorbidity and the impact of social support on multimorbidity. Methods: A total of 9168 valid samples, with an average age of 59.60 years, were included in the study. Using the social support-related variables of the respondents, we conducted factor analysis and constructed regression models of common factors of social support and multimorbidity-related outcomes, intending to analyze the impact of common factors of social support on multimorbidity in the middle-aged and older adults. Results: The multimorbidity of middle-aged and older adults in China was related to multiple factors of social support, and the differences were statistically significant. Logistic regression showed that social support in the form of activity/recreational facilities and medical resources was a protective factor of multimorbidity, that family emotional support and economic support had a positive effect on life satisfaction of comorbid patients, and that social support in the form of education, social life and housing conditions was negatively correlated with catastrophic medical expenditure of the comorbid population ( P<0.05). Conclusion: Social support for middle-aged and older adults in China is unevenly distributed. Social support in the form of activity/recreational facilities and medical resources may reduce the risks of multimorbidity among middle-aged and older adults. Good family economic and emotional support can improve the life satisfaction of middle-aged and older adults with multimorbidity. Social support in the form of education, social life and housing conditions may reduce the risk of catastrophic medical expenditure in middle-aged and older adults with multimorbidity.

[Subacute Thyroiditis Following HPV Vaccination: A Case Report].

Subacute thyroiditis (SAT) is the most common self-limiting thyroid disease causing pain. The etiology of the disease remains unknown, but it is usually related to viral infection or allergic reaction after viral infection. SAT after vaccination is extremely rare. The patient had a fever of no clearly defined cause about 8 hours after receiving the first dose of a 0.5 mL 9-valent human papillomavirus vaccine (Gardasil 9). The highest temperature was 37.8 ℃, accompanied by a pain in the neck, fatigue and the increasing pain when swallowing. After the patient was admitted to the hospital, physical examination revealed Ⅱ° enlargement of the thyroid gland, which was hard and tender, and no vascular murmur was heard. There was no redness, swelling or ulceration at the vaccination site, and no obvious abnormalities were observed in other physical examinations. Laboratory findings were as follows: C-reactive protein, 25.20 mg/L; erythrocyte sedimentation rate, 55 mm/1 h; leukocyte, 4.94×10 9 L -1; thyrotropin, 0.137 mU/L; free thyroxine, 22.32 pmol/L; antithyroglobulin antibody, 69.18 IU/mL; anti-thyroid peroxidase antibody, 21.66 IU/mL. Thyroid ultrasonography showed diffuse enlargement of bilateral thyroid with uneven internal echo. The patient was diagnosed with SAT. After 5 days of treatment with ibuprofen, the patient no longer had low fever and the neck pain was relieved. The patient was followed up till now, and had completed the vaccination of the three-dose 9-valent human papillomavirus vaccine. The function of thyroid was found to be normal in follow-up visits, and SAT did not recur.

Structural and Functional Insights into PpgL, a Metal-Independent ß-Propeller Gluconolactonase That Contributes to Pseudomonas aeruginosa Virulence.

Biofilm formation is a critical determinant in the pathopoiesis of Pseudomonas aeruginosa It could significantly increase bacterial resistance to drugs and host defense. Thus, inhibition of biofilm matrix production could be regarded as a promising attempt to prevent colonization of P. aeruginosa and the subsequent infection. PpgL, a periplasmic gluconolactonase, has been reported to be involved in P. aeruginosa quorum-sensing (QS) system regulation. However, the detailed function and catalysis mechanism remain elusive. Here, the crystal structure of PpgL is described in the current study, along with biochemical analysis, revealing that PpgL is a typical ß-propeller enzyme with unique metal-independent lactone hydrolysis activity. Consequently, comparative analysis of seven-bladed propeller lactone-catalyzing enzymes and mutagenesis studies identify the critical sites which contribute to the diverse catalytic and substrate recognition functions. In addition, the reduced biofilm formation and attenuated invasion phenotype resulting from deletion of ppgL confirm the importance of PpgL in P. aeruginosa pathogenesis. These results suggest that PpgL is a potential target for developing new agents against the diseases caused by P. aeruginosa.

Cisplatin inhibits the progression of bladder cancer by selectively depleting G-MDSCs: A novel chemoimmunomodulating strategy.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.

Systemic immune-inflammation index and all-cause and cause-specific mortality in sarcopenia: a study from National Health and Nutrition Examination Survey 1999-2018.

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

SUMO-specific protease 2 suppresses cell migration and invasion through inhibiting the expression of MMP13 in bladder cancer cells.

BACKGROUND: SUMO-specific protease 2 (SENP2) is a de-SUMOylation protease family member which has an indispensable role in the regulation of NF-κB transcriptional activation and Wnt signaling. However, whether SENP2 plays a role in tumor metastasis is completely unknown. METHODS: Real-time PCR and Western blot was used to detect the expression of SENP2 in human bladder cancer samples and cell lines. Small interfering RNA (siRNA) was used to silencing the expression of SENP2. Matrigel-coated invasion chambers were used to detect the invasion ability of SENP2 in bladder cancer cells. RESULTS: SENP2 was down-regulated in bladder cancer samples. SENP2 inhibited bladder cancer cells migration and invasion in vitro. Transcriptional analysis of several genes associated with tumor metastasis and invasion demonstrated that SENP2 selectively down-regulated MMP13 in bladder cancer cells. Further analysis indicated that silencing of MMP13 rescued the invasive phenotype in SENP2 expressing T24 cells. CONCLUSION: SENP2 functions as a tumor metastasis suppressor in bladder cancer. The effects of SENP2 on bladder cancer invasion are partially mediated by inhibiting the expression of MMP13.

RS 504393 inhibits M-MDSCs recruiting in immune microenvironment of bladder cancer after gemcitabine treatment.

Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients.

Preoperative CD4+CD25+/CD4+ and tumor diameter predict prognosis in male patients with bladder cancer.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

miRNA­26a­5p and miR­26b­5p inhibit the proliferation of bladder cancer cells by regulating PDCD10.

MicroRNA (miR)­26a­5p and miR­26b­5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR­26a­5p and miR­26b­5p were lower than in paired normal tissues. The upregulation of miR­26­5p significantly inhibited the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) was the downstream target gene of miR­26a­5p/miR­26b­5p, and this was ascertained by western blotting and quantitative real­time reverse transcription PCR (RT­qPCR). In addition, in the 3'­UTR of PDCD10, the binding site was identified using a luciferase reporter assay. We determined that clinical BC tissues presented higher PDCD10 levels than adjacent normal tissues and that PDCD10 promoted proliferation of BC cell lines. Overexpression of miR­26a­5p/miR­26b­5p inhibited the stimulatory effect on proliferation of BC cells induced by PDCD10. In addition, in vivo experiments and clinical data revealed that the prognosis of BC patients with high expression of miR­26a­5p/miR­26b­5p and low expression of PDCD10 was better than that of patients with low miR­26­5p and high PDCD10 expression. These data revealed that miR­26a­5p and miR­26b­5p were pivotal regulators in BC progression by targeting the proliferation­related protein, PDCD10. The miR­26­5p/PDCD10 interaction may provide important insight into the pathway of BC progression and present novel opportunities for future diagnosis and treatment strategies, especially for patients with high levels of PDCD10.