Determination of COL1A1-PDGFB breakpoints by next-generation sequencing in the molecular diagnosis of dermatofibrosarcoma protuberans.

OBJECTIVE: In most cases, dermatofibrosarcoma protuberans (DFSP) is characterized by the chromosomal translocation t (17; 22) (q22; q13) that leads to a fusion of collagen type 1 alpha 1 (COL1A1) and platelet-derived growth factor beta chain (PDGFB). Recently, next-generation sequencing (NGS) has been reported to detect fusion transcripts in some malignancies. Therefore, the present study aimed to evaluate the utility of the targeted NGS in detecting the COL1A1-PDGFB fusion in patients with DFSP. METHODS: We designed a targeted DNA capture panel to tile along the fusion regions, including exon, intron, and untranslated regions of the COL1A1 and PDGFB. A cohort of 18 DNA samples extracted from formalin-fixed, paraffin-embedded tissues was used to evaluate the targeted NGS. The results were compared with that of fluorescence in situ hybridization (FISH). RESULTS: The COL1A1-PDGFB fusion was identified in 13 of 18 cases (72.2%) by targeted NGS assay. PDGFB breakpoints were constantly found in exon 2, while breakpoints in COL1A1 varied from exon 15 to 46. Of these 18 cases assayed by FISH, 12 (66.7%) exhibited COL1A1-PDGFB fusion signals. One case (P9), which was FISH-negative, was demonstrated with the fusion by targeted NGS and validated by PCR and Sanger sequencing. The targeted NGS results showed a high concordance with the results of the FISH assay (94.4%). CONCLUSION: Our study reported a targeted NGS assay for detecting the breakpoints of the COL1A1-PDGFB fusion gene, which can be implemented in diagnosing patients with DFSP.

Imaging findings of Bowen's disease: A comparison between ultrasound biomicroscopy and conventional high-frequency ultrasound.

OBJECTIVES: To compare the imaging findings of Bowen's disease (BD) between ultrasound biomicroscopy (UBM) and conventional high-frequency ultrasound (HFUS). METHODS: A total of 29 pathologically proven BD lesions in 28 patients were retrospectively enrolled in the study, and all were after surgery. All the lesions were imaged with both UBM and HFUS. The imaging features on HFUS and UBM were analyzed and compared. The diagnostic results of ultrasound for BD were referenced with pathology results. RESULTS: All the 29 (100%) BD lesions appeared hypoechogenicity, solid component, and superficial hyperechoic layer (ie, keratinization) on both UBM and HFUS. The typical imaging feature of BD lesions, that was, infiltration depth confined to the epidermis, was visualized in 25 (86.2%, 25/29) lesions on UBM whereas 15 (51.7%, 15/29) on HFUS (P = .002). A "wave sign," which corresponds to the surface keratinization of BD lesion, was visualized in 17 (58.6%, 17/29) of BD lesions on UBM whereas 6 (20.7%, 6/29) on HFUS (P = .001). UBM and HFUS correctly diagnosed 25 (86.2%, 25/29) and 15 (51.7%, 15/29) BD lesions, respectively (P = .002). CONCLUSIONS: Bowen's disease has some typical imaging features on US. The "wave sign" of the superficial hyperechoic layer and the clear borderline between the tumor in epidermis and the slightly hyperechoic dermis layer are better depicted by UBM in comparison with HFUS, which leads to a more accurate diagnosis of BD. UBM has potential to be used as a diagnostic tool for characterization of BD on account of its high resolution.

Ultrasound Biomicroscopy and High-Frequency Ultrasound for Evaluating Extramammary Paget Disease With Pathologic Correlation.

OBJECTIVES: The purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high-frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings. METHODS: In this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS. RESULTS: Ultrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P < .001). Additionally, the layer involvement of 15 lesions (88.2%) on UBM was consistent with the pathologic results (κ = 0.746). High-frequency ultrasound revealed profuse blood flow in most lesions (64.7% [11 of 17]), and 1 case showed inguinal lymph node metastasis. CONCLUSIONS: Combined use of UBM and HFUS can provide key information on EMPD based on ultrasound features. Comparatively, UBM provides clearer morphologic information, whereas HFUS provides information on lymph node metastasis and blood flow.

Curcumin Alleviates Epidermal Psoriasis-Like Dermatitis and IL-6/STAT3 Pathway of Mice.

Background: To further investigate why curcumin (CUR) can attenuate psoriasis-like dermatitis of mice. Methods and Results: Sixteen mice were randomized into four groups. The control group used carrier cream, and the model and the CUR group were applied with topical 5% imiquimod in the naked mice skin once a day for 6 days (62.5 mg/day/mice). Meanwhile, the control and model mice were given the same dose of saline by oral means, while mice in the CUR groups received oral drug doses of 50 and 100 mg/kg once a day for 6 days, respectively. CUR could largely improve imiquimod-induced lesions of mice. By using the ELISA and qPCR, we found that the protein and mRNA levels of epidermal TNF-α and IL-6 were inhibited by CUR. The phosphorylation levels of STAT3 and its downstream associated protein levels (eg, Cyclin D1, Bcl-2 and Pim1) in skin tissues of different groups were also inhibited by CUR. Furthermore, the results of immunohistochemistry also showed the repressed effect of CUR for the expression of TNF-α, IL-6 and p-STAT3 in psoriasis-like lesions of mice. Conclusion: CUR can effectively ameliorate the featured lesions of psoriasis mice, which may be closely associated with the involvement of IL-6/STAT3 signaling.

Chinese patent medicine for osteoporosis: a systematic review and meta-analysis.

Chinese patent medicine (CPM) has been widely used in China for patients with osteoporosis (OP) but a comprehensive literature review is still important. Therefore, we performed meta-analysis using six electronic databases prior to 30 April 2021 only randomized controlled trials (RCTs) using CPM as the first-line treatment in adults with OP were included. Thirty RCTs met the inclusion criteria with a total of 2723 patients, and seven types of CPM were included. Compared with the control group, 23 studies showed significantly improved bone mineral density (BMD) (lumbar spine) (mean difference [MD] = 0.08; confidence interval [CI], 0.03 to 0.13), 15 studies showed significantly improved BMD (femoral) (MD = 0.05; 95% CI, 0.02 to 0.07), 6 studies showed significantly improved BMD (radius) (MD = 0.06; 95% CI, 0.03 to 0.09), 2 trials showed significantly improvement of BMD (ulna) (MD = 0.02; 95% CI, 0.01 to 0.03), and 4 trials showed significantly improved BMD (MD = 0.09; 95% CI, 0.09 to 0.10). The meta-analysis also showed that CPM had superior pain improvement, a higher total effectiveness rate, and a lower risk of adverse events compared with standard western treatment. The findings of this study suggest that CPM therapy may be a safe and effective alternative treatment modality for OP, it has potential benefits in relieving symptoms and improving BMD compared to western medications or placebos.

Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1.

Purpose: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR). Methods: The antidiabetic effect of RR was studied in Streptozocin (STZ)-induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG). Results: After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)-components-disease (DM)-targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The TRPV1 overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while SCD1 overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 µg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively. Conclusion: In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.

General recommendation for assessment and management on the risk of glucocorticoid-induced osteonecrosis in patients with COVID-19.

BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disaster in human medical history and glucocorticoids remain the most promising therapy. Osteonecrosis is a disease caused by reduced intraosseous blood flow to bones in the joints, which will rapidly induce joint destruction. Approximately one-third patients with severe acute respiratory syndrome (SARS) who received high cumulative doses and long treatment durations of glucocorticoids occurred osteonecrosis. Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics, and therapeutic strategies, it is particularly desirable to investigate whether osteonecrosis will become a common sequela among convalescent COVID-19 patients. METHODS: This multi-strategy study was designed by integrating different research methods, such as meta-analysis, systematic review, and cross-sectional investigations to address above study objectives. At first, two meta-analyses were performed on the osteonecrosis incidence among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in Wuhan city of China were also conducted. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis patients with COVID-19 infection were further presented and discussed. RESULTS: Our meta-analysis showed that 32% of SARS patients had developed osteonecrosis after receiving glucocorticoid treatment with high dose, and our system review supported that low level glucocorticoid exposure might also lead to the occurrence of osteonecrosis. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in Wuhan city of China found that the average of cumulative glucocorticoid exposure level was 504 â€‹mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case was identified from 1406 patients with COVID-19 during our cross-sectional investigation, implying that preventive management of osteonecrosis should be better started with regular clinical follow-up observation. CONCLUSION: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to establish risk-classification-based early screening and to introduce early prevention protocol of its associated osteonecrosis that will be of clinical significance in favor of improved prognosis of this disease. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To establish risk-classification-based early screening and to introduce early prevention protocol of glucocorticoid-induced osteonecrosis will be of clinical significance in favor of improved prognosis of COVID-19.

A novel large deletion of the CYLD gene causes CYLD cutaneous syndrome in a Chinese family.

BACKGROUND: CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) is a rare autosomal dominant hereditary disease characterized by multiple adnexal skin tumors including cylindromas, spiradenomas, and trichoepitheliomas. More than 100 germline mutations of the cylindromatosis (CYLD) gene have been reported in CCS and most of them are frameshift mutations or small alterations. METHODS: We identified a large, three-generation Chinese family with CCS, which consisted of 18 living family members, including six affected individuals. To explore the molecular biology of this family, we carried out targeted next-generation sequencing and Affymetrix CytoScan HD SNP array to analyze the mutation in the CYLD gene. RESULTS: A novel large deletion mutation, NC_000016.9:g.(50826498_50827517)_(50963389-50967346)del was found in the proband of this family. This deletion results in the loss of a nearly 140 kb fragment of the CYLD gene, spanning exons 17 ~ 20, which represent the coding regions of the ubiquitin-specific protease domain. Further quantitative polymerase chain reaction proved that all patients and two proband-related family members carried this large deletion. CONCLUSIONS: Our study expands the types of mutations in CCS and will undoubtedly provide valuable information for genetic counseling for families affected by the condition.

Acupotomy Therapy for Knee Osteoarthritis Pain: Systematic Review and Meta-Analysis.

METHODS: We performed a comprehensive search on PubMed, the Cochrane Library, EMBASE, and four Chinese databases for articles published prior to June 2020. We included only randomized controlled trials (RCTs) that used acupotomy therapy as the major intervention in adults with knee OA, were published in either Chinese and English, included more than 20 subjects in each group, and included pain and function in the outcome measures. Knee OA was defined by the American College of Rheumatology or Chinese Orthopedic Association criteria in all studies. We extracted the visual analogue scale (VAS) pain score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the total effectiveness rate, the modified Japanese Orthopedic Association (JOA) activities of daily living score, and Lysholm's score. We calculated the mean difference (MD) or risk ratio (RR) for all relevant outcomes. Meta-analyses were conducted using random-effects models when appropriate. RESULTS: We identified 1317 potentially relevant studies, thirty-two of which met the eligibility criteria and were conducted in China between 2007 and 2020. A total of 3021 knee OA patients (62.96% female, median age: 57 years, and median disease duration: 33 months) were included. The treatment duration ranged from 1 week to 5 weeks (median: 3 weeks). The typical acupotomy treatment involved releasing soft tissue adhesions and was performed once a week for 1-5 weeks until the pain was relieved. The control group treatments included acupuncture (8 studies), electroacupuncture (10 studies), sodium hyaluronate (8 studies), radiofrequency electrotherapy (1 study), and nonsteroidal anti-inflammatory drugs (NSAIDs, 5 studies). The results from the meta-analysis showed that acupotomy led to superior improvements in the VAS pain score (MD = -1.11; 95% confidence interval (CI), -1.51 to -0.71; p < 0.00001) and WOMAC pain score (MD = -2.32; 95% CI, -2.94 to -1.69; p < 0.00001), a higher total effectiveness rate (RR = 1.15; 95% CI, 1.09-1.21; p < 0.00001), and superior improvements in the JOA score (MD = 6.39; 95% CI, 4.11-9.76; p < 0.00001) and Lysholm's score (MD = 12.75; 95% CI, 2.61-22.89; p = 0.01) for overall pain and function. No serious adverse events were reported. CONCLUSION: Chinese acupotomy therapy may relieve pain and improve function in patients with knee OA. Furthermore, rigorously designed and well-controlled RCTs are warranted.

Exploring the Risk Factors for the Misdiagnosis of Osteonecrosis of Femoral Head: A Case-Control Study.

OBJECTIVE: The purpose of the present study was to evaluate the present situation and risk factors for the misdiagnosis of osteonecrosis of femoral head (ONFH), providing the basis for accurate diagnosis of ONFH. METHODS: For this retrospective study, 1471 patients with ONFH were selected from the China Osteonecrosis of Femoral Head Database (CONFHD). These patients had been recruited between July 2016 and December 2018. According to whether or not they were misdiagnosed, the patients were divided into two groups, with 1168 cases (22-84 years old) included in the diagnosis group and 303 cases (21-80 years old) in the misdiagnosis group. Misdiagnosis was measured using the following criteria: (i) the patient had the same symptoms and signs, and the second diagnosis was not consistent with the initial diagnosis within 6 months; and (ii) the patient was admitted to a hospital participating in CONFHD and the previous diagnosis was inconsistent with the diagnosis given by the expert group. Comparisons of age, visual analogue scale for pain, and body mass index between the two groups were performed using a t-test. Gender, causes of ONFH, primary diseases requiring corticosteroids, methods of corticosteroid use, corticosteroid species, type of trauma, onset side of the disease, pain side, whether symptoms are hidden, and type of imaging examination at the initial visit were compared using the χ2 -test. Years of alcohol consumption, weekly alcohol consumption, and physician title at the initial visit were compared using a Mann-Whitney U-test. Furthermore, the statistically significant factors were evaluated using multiple regression analysis to investigate the risk factors of misdiagnosis. RESULTS: A total of 303 patients (20.6%) were misdiagnosed: 118 cases were misdiagnosed as lumbar disc herniation, 86 cases as hip synovitis, 48 cases as hip osteoarthritis, 32 cases as rheumatoid arthritis, 11 cases as piriformis syndrome, 5 cases as sciatica, and 3 cases as soft-tissue injury. Whether symptoms are hidden (P = 0.038, odds ratio [OR] = 1.546, 95% confidence interval [CI] = 1.025-2.332), physician title at the initial visit (P < 0.001, OR = 3.324, 95% CI = 1.850-5.972), X-ray examination (P < 0.001, OR = 4.742, 95% CI = 3.159-7.118), corticosteroids (P < 0.001, OR = 0.295, 95% CI = 0.163-0.534), alcohol (P < 0.001, OR = 0.305, 95% CI = 0.171-0.546), and magnetic resonance imaging (MRI) examination (P = 0.042, OR = 0.649, 95% CI = 0.427-0.985) were each found to be associated with misdiagnosis. CONCLUSION: Osteonecrosis of the femoral head is easily misdiagnosed as lumbar disc herniation, hip synovitis, hip osteoarthritis, and rheumatoid arthritis. Patient history of corticosteroid use or alcohol abuse and MRI examination at the initial diagnosis may be protective factors for misdiagnosis. Hidden symptoms, physician title at the initial visit (as attending doctor or resident doctor), and only X-ray examination at the initial diagnosis may be risk factors for misdiagnosis.