Pathological findings with vacuoles in anti-mitochondrial antibody-positive inflammatory myopathy.

BACKGROUND: A few patients with inflammatory myopathy showed anti-mitochondrial antibody (AMA) positivity. This study aimed to report the clinical and pathological findings with vacuoles in 3 cases of such patients. METHODS: Three cases with myositis from the Myositis Clinical Database of Peking University First Hospital were identified with AMA positivity. Their clinical records were retrospectively reviewed and the data was extracted. All the 3 cases underwent muscle biopsy. RESULTS: Three middle-aged patients presented with chronic-onset weakness of proximal limbs, marked elevation of creatine kinase, and AMA-positivity. Two of the 3 cases meet the criteria of primary biliary cholangitis. All the 3 cases presented with cardiac involvement and proteinuria. Two cases developed type 2 respiratory failure. MRI of the thigh muscle showed multiple patches of edema bilaterally in both cases, mostly in the adductor magnus. Pathological findings include degeneration of muscle fibers, diffused MHC-I positivity, and complement deposits on cell membranes. Vacuoles without rims of different sizes were discovered under the membrane of the muscle fibers. A few RBFs were discovered in case 1, while a diffused proliferation of endomysium and perimysium was shown in case 2. CONCLUSIONS: AMA-positive inflammatory myopathy is a disease that could affect multiple systems. Apart from inflammatory changes, the pathological findings of muscle can also present vacuoles.

A DNA nanostructure-Hif-1α inducer complex as novel nanotherapy against cisplatin-induced acute kidney injury.

Since its discovery in 1978, cisplatin-based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin-induced acute kidney injury (AKI), which occurs in 30% of cisplatin-treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin-induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA-nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG-4592, a novel Hif-1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG-4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin-induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA-based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug-induced kidney injury, leading to improved clinical outcomes.

A prospective study of the prostate health index density and multiparametric magnetic resonance imaging in diagnosing clinically significant prostate cancer.

PURPOSE: To evaluate the predictive performance of the prostate health index (PHI) and PHI density (PHID), for clinically significant prostate cancer (csPCa) in patients with a PI-RADS score ≤3. MATERIALS AND METHODS: Patients tested for total prostate-specific antigen (tPSA, ≤100 ng/mL), free PSA (fPSA), and p2PSA at Peking University First Hospital were prospectively enrolled. Possible predictive factors of csPCa were analyzed using the receiver operating characteristic (ROC) curve. Results were expressed as area under the curve (AUC) with 95% confidence intervals (CI). The cutoff values of PHI and PHID were determined. RESULTS: We enrolled 222 patients in this study. The prevalence of csPCa in the PI-RADS ≤3 subgroup (n=89) was 22.47% (20/89). Age, tPSA, F/T, prostate volume, PSA density, PHI, PHID, and PI-RADS score were significantly associated with csPCa. PHID (AUC: 0.829 [95% CI: 0.717-0.941]) was the best predictor of csPCa. PHID >0.956 was set as the threshold of suspicious csPCa with a sensitivity of 85.00% and a specificity of 73.91%, avoiding 94.44% of unnecessary biopsies but missing 15.00% csPCa. A threshold of PHI ≥52.83 showed the same sensitivity but a rather lower specificity of 65.22% that avoided 93.75% of unnecessary biopsies. CONCLUSIONS: PHI and PHID have the best predictive performance of csPCa in patients with PI-RADS score ≤3. A threshold value of PHID ≥0.956 may be used as the criterion for biopsy in these patients.

Age-related morphometrics of normal adrenal glands based on deep learning-aided segmentation.

OBJECTIVE: This study aims to evaluate the morphometrics of normal adrenal glands in adult patients semiautomatically using a deep learning-based segmentation model. MATERIALS AND METHODS: A total of 520 abdominal CT image series with normal findings, from January 1, 2016, to March 14, 2019, were retrospectively collected for the training of the adrenal segmentation model. Then, 1043 portal venous phase image series of inpatient contrast-enhanced abdominal CT examinations with normal adrenal glands were included for analysis and grouped by every 10-year gap. A 3D U-Net-based segmentation model was used to predict bilateral adrenal labels followed by manual modification of labels as appropriate. Quantitative parameters (volume, CT value, and diameters) of the bilateral adrenal glands were then analyzed. RESULTS: In the study cohort aged 18-77 years old (554 males and 489 females), the left adrenal gland was significantly larger than the right adrenal gland [all patients, 2867.79 (2317.11-3499.89) mm3 vs. 2452.84 (1983.50-2935.18) mm3, P < 0.001]. Male patients showed a greater volume of bilateral adrenal glands than females in all age groups (all patients, left: 3237.83 ± 930.21 mm3 vs. 2646.49 ± 766.42 mm3, P < 0.001; right: 2731.69 ± 789.19 mm3 vs. 2266.18 ± 632.97 mm3, P = 0.001). Bilateral adrenal volume in male patients showed an increasing then decreasing trend as age increased that peaked at 38-47 years old (left: 3416.01 ± 886.21 mm3, right: 2855.04 ± 774.57 mm3). CONCLUSIONS: The semiautomated measurement revealed that the adrenal volume differs as age increases. Male patients aged 38-47 years old have a peaked adrenal volume.

Cutoff Values of Prostate Imaging Reporting and Data System Version 2.1 Score in Men With Prostate-specific Antigen Level 4 to 10 ng/mL: Importance of Lesion Location.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has been shown to have a good performance in predicting cancer among patients with a prostate-specific antigen (PSA) level of 4 to 10 ng/mL. However, lesion location on mpMRI has never been separately considered. PATIENTS AND METHODS: Patients with PSA level of 4 to 10 ng/mL were prospectively enrolled and underwent transrectal ultrasound-guided prostate biopsy. Patient information was collected, and logistic regression analysis was performed to determine the predictive factors of clinically significant prostate cancer (csPCa). Patients were grouped by lesion location to determine the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 cutoff value in predicting csPCa. RESULTS: Among 222 patients, 121 were diagnosed with PCa and 92 had csPCa. Age, prostate volume, PSA density, location (peripheral zone, csPCa only), and PI-RADS v2.1 score were correlated with PCa and csPCa, and PI-RADS v2.1 score was the best predictor. A PI-RADS v2.1 score of 4 was the best cutoff value for predicting csPCa in patients with lesions only in the transitional zone with respect to the Youden index (0.5896) and negative predictive value (93.10%) with acceptable sensitivity (81.82%) and specificity (77.14%). An adjustment of the cutoff value to 3 for lesions in the peripheral zone would increase the negative predictive value (92.00%) and decrease the false negative rate (2.90%) with an acceptable sensitivity (97.10%) and specificity (30.67%). CONCLUSION: PI-RADS v2.1 score is an effective predictor of csPCa in patients with PSA levels of 4 to 10 ng/mL. Patients with transitional zone or peripheral zone lesions should undergo biopsy if the PI-RADS v2.1 score is ≥ 4 or ≥ 3, respectively.

[Killing effect of ZnPcH(1)-PDT on lymphoma cells].

The objective of this study was to investigate the effect of ZnPcH(1)-PDT on the lymphoma cells and its mechanism. Human Burkitt's lymphoma cell line CA46 and mouse lymphoma cell line P388 were selected as objects for study. The killing effect of ZnPcH(1)-PDT on cells were assessed by MTT method and colony formation assay; the cell death patterns were analyzed by AO/EB fluorescence stain, TdT-mediated dUTP nick end labeling (TUNEL), DNA ladder assay; and the different proportions of each death pattern were determined by Annexin-V(-FITC)/PI double stains. The results showed that ZnPcH(1)-PDT displayed anti-proliferation effect on both CA46 cells and P388 cells in dose-dependent manner. CA46 cells were less sensitive to PDT than P388 cells (p < 0.05). Furthermore, PDT could induce cell apoptosis in time-dependent manner. The rate of cell apoptosis increased in the PDT-treated cells. The results of Annexin-V(-FITC)/PI stain indicated that early apoptosis was the main death pattern in the PDT-treated CA46 cells, while early apoptosis and necrosis were the main death model in the PDT-treated P388 cells. It is concluded that ZnPcH(1)-PDT can effectively inhibit lymphoma cell proliferation and induce cell apoptosis.