Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Distinctive magnetic resonance imaging features in primary central nervous system lymphoma: A case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare malignant tumor originating from the lymphatic hematopoietic system. It exhibits unique imaging manifestations due to its biological characteristics. CASE SUMMARY: Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and magnetic resonance spectroscopy was performed. The imaging findings showed multiple space-occupying lesions with low signal on T1-weighted imaging, uniform high signal on T2-weighted imaging, and obvious enhancement on contrast-enhanced scans. DWI revealed diffusion restriction, PWI demonstrated hypoperfusion, and spectroscopy showed elevated choline peak and decreased N-acetylaspartic acid. The patient's condition significantly improved after hormone shock therapy. CONCLUSION: This case highlights the distinctive imaging features of PCNSL and their importance in accurate diagnosis and management.

MKRN1 promotes colorectal cancer metastasis by activating the TGF-ß signalling pathway through SNIP1 protein degradation.

BACKGROUND: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. METHODS: MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. RESULTS: MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-ß (TGF-ß) signalling, and MKRN1 promotes TGF-ß signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group. CONCLUSIONS: High MKRN1 levels promote TGF-ß signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-ß axis may be a potential therapeutic target in CRC.

Efficacy and safety of microwave ablation for the treatment of multifocal versus unifocal T1N0M0 papillary thyroid carcinoma: a propensity-matched multicentre retrospective study.

OBJECTIVES: Microwave ablation (MWA) has been widely used for unifocal papillary thyroid carcinoma (U-PTC) and has recently been preliminarily used in multifocal papillary thyroid carcinoma (M-PTC). However, the efficacy and safety of MWA for M-PTC have not been investigated in large samples. The aim of the present study was to evaluate the efficacy and safety of MWA for M-PTC and compare them with MWA for U-PTC. MATERIALS AND METHODS: This retrospective multicentre study enrolled 504 patients (376 females) who underwent MWA for U-PTC (340 cases) or M-PTC (164 cases) from Jan 2015 to Dec 2020. The median age of the patients was 43 years (age range, 20-80 years). Propensity score matching (PSM) was used to balance the baseline characteristics between M-PTC group and U-PTC group. The tumour progression, tumour disappearance, and complication rates were compared between the two groups. RESULTS: The complete ablation was achieved in all enrolled cases in one session. According to the statistical results, no significant differences were shown in tumour progression-free survival (p  = 0.29) or cumulative tumour progression rate (6.7% vs. 4.3%, p  = 0.33) between the M-PTC and U-PTC groups during the follow-up time. However, the tumour disappearance rate in the M-PTC group was lower in the U-PTC group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the M-PTC group (p < 0.001). The complication rate showed no significant difference (3.0% vs. 4.9%, p  = 0.571). CONCLUSIONS: MWA is an effective and safe treatment for selected patients with M-PTC, and the prognosis is similar to that of U-PTC. CLINICAL RELEVANCE STATEMENT: The present study provided evidence that compared with unifocal papillary thyroid cancer, microwave ablation could also treat multifocal T1N0M0 papillary thyroid cancer safely with similar clinical outcome, which could promote the application of minimally invasive treatment for papillary thyroid cancer. KEY RESULTS: • Microwave ablation for multifocal and unifocal T1N0M0 papillary thyroid carcinoma had similar tumour progression rates after propensity score matching (6.7% vs. 4.3%, p = 0.33). • The tumour disappearance rate in the multifocal group was lower than that in the unifocal group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the multifocal group (p < 0.001). • Tumour size, number, and location were not risk factors for tumour progression in the multifocal papillary thyroid cancer group.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Insulin Resistance and the Prognosis in Diffuse Large B-cell Lymphoma.

OBJECTIVE:  To investigate whether insulin resistance (IR) affects the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Place and Duration of the Study: The Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from September 2017 to December 2021. METHODOLOGY: This study retrospectively analysed 324 patients with DLBCL who were divided into a non-IR group (251 cases) and IR group (73 cases) according to IR. The authors collected clinical data of the study population and calculated the overall survival (OS) of patients through inpatient case data or follow-up. The Cox regression method was used to assess the prognostic factors of the patients. The Kaplan-Meier method was used for drawing the survival curve of IR on OS of the DLBCL patients. RESULTS: The IR group had older age, higher international prognostic index (IPI), later stage, and higher insulin levels. The five-year OS rate was 46% in the IR group and 66% in the non-IR group. Compared with the non-IR group, the IR group showed a poor prognosis (OS: adjusted HR 1.23, 95% CI: 1.02-1.41, p = 0.031). CONCLUSION: IR was one of the factors leading to poor prognosis in patients with DLBCL, and attention should be paid to this risk factor. KEY WORDS: Insulin resistance, Diffuse large B-cell lymphoma, Overall survival, Prognosis.

Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study.

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179.

Exosomal miR-150 derived from BMSCs inhibits TNF-α-mediated osteoblast apoptosis in osteonecrosis of the femoral head by GREM1/NF-κB signaling.

Aim: The purpose of this study was to investigate the functions of exosomal miR-150 derived from bone marrow mesenchymal stem cells in osteonecrosis of the femoral head (ONFH). Materials & methods: Cell viability and apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Alizarin red staining was performed to detect calcium deposits. A rat model was established to assess the effects of exosomal miR-150 on ONFH in vivo. Results: Exosomes or exosomal miR-150 derived from bone marrow mesenchymal stem cells inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy. Exosomal miR-150 suppressed apoptosis and induced autophagy in TNF-α-treated osteoblasts by regulating the GREM1/NF-κB axis. Exosomal miR-150 also improved the pathological features of ONFH in vivo. Conclusion: Exosomal miR-150 alleviates ONFH by mediating the GREM1/NF-κB axis. This study provides a potential therapeutic strategy for ONFH.

Osteonecrosis of the femoral head (ONFH) is an orthopedic disease that frequently occurs in young adults aged less than 50 years. At present, there is no widely accepted curative surgical procedure or drug therapy for this disease. Bone marrow mesenchymal stem cells (BMSCs) play a key role in the progression of ONFH. BMSC-derived exosomes refer to small membrane vesicles that can transfer proteins, miRNAs and mRNAs, which are closely related to the development of ONFH. This study showed that exosomal miRNA-150 derived from BMSCs inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy by regulating the GREM1/NF-κB axis. In addition, exosomal miRNA-150 alleviated the symptoms of ONFH in rats.

Internal Jugular Vein Thrombosis After Microwave Ablation of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Case Report.

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang's team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.

Factors related to the absorption rate of benign thyroid nodules after image-guided microwave ablation: a 3-year follow-up.

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.

[Analysis of Clinical Characteristics of JAK2 V617F and BCR-ABL Double-Mutant Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.

Efficacy of an Yinyanghuo (Herba Epimedii Brevicornus)-Xianmao (Rhizoma Curculiginis) drug pair in a rat model of polycystic ovary syndrome.

OBJECTIVE: To identify active compounds in an Yinyanghuo (Herba Epimedii Brevicornus) - Xianmao (Rhizoma Curculiginis) drug pair (ECD) and investigate its efficacy on polycystic ovary syndrome (PCOS), and its possible mechanism in a rat model of PCOS. METHODS: A network pharmacology approach involving a characteristic drug assessment, active compound and target prediction, PCOS gene collection as well as network analysis was employed. The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target. RESULTS: Six networks were constructed, an active compound-target network for the ECD (C-T network), a drug-target network (D-T network), a related genes network, a targets interaction network, a key genes interaction network, and a gene-pathway network. A total of 41 compounds and 261 targets were identified for the ECD, 232 PCOS-related genes, 31 cogenes, and 14 pathways. These pathways may be involved in the efficacy of ECD on PCOS. The proteins most involved in the signal pathways for all targets were AKT1, IL6, INSR, ESR, and GSK3B. The AKT1 target was selected for experimental verification. Based on the Western blot and real-time PCR results, the expression of AKT1 in the PCOS model varied after treatment with ECD. CONCLUSIONS: Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS. AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

Impact of Prior Digestive System Disease on In-Hospital Gastrointestinal Bleeding in Patients with Acute Myocardial Infarction.

OBJECTIVE: Patients presenting with acute myocardial infarction (AMI) with prior digestive system disease are more likely to suffer from gastrointestinal (GI) bleeding than those without these diseases. However, few articles reported how the different conditions of the digestive tract produced different risks of GI bleeding. METHODS: A single-center study on 7464 patients admitted for AMI from December 2010 to June 2019 in the Beijing Chaoyang Heart Center was retrospectively examined. Patients with major GI bleeding (n = 165) were compared with patients without (n = 7299). Univariate and multivariate logistic regression models were constructed to test the association between GI bleeding and prior diseases of the digestive tract, including gastroesophageal reflux disease, chronic gastritis, peptic ulcer, hepatic function damage, diseases of the colon and rectum, and gastroenterological tract tumors. RESULTS: Of the 7464 patients (mean age, 63.4; women, 25.6%; STEMI, 58.6%), 165 (2.2%) experienced major GI bleeding, and 1816 (24.3%) had a history of digestive system disease. The risk of GI bleeding was significantly associated with peptic ulcer (OR = 4.19, 95% CI: 1.86-9.45) and gastroenterological tumor (OR = 2.74, 95% CI: 1.07-7.04), indicated by multivariate logistic regression analysis. CONCLUSION: Preexisting peptic ulcers and gastroenterological tract tumors rather than other digestive system diseases were indicators of gastrointestinal bleeding in patients with AMI who undergo standard antithrombotic treatment during hospitalization.

Distally Based Perforator-Plus Sural Neurocutaneous Flap with High or Low Pivot Point: Anatomical Considerations and a Retrospective Study of a Clinical Series of 378 Flaps.

BACKGROUND: This study is to describe the distribution of natural true anastomoses associated with the distally based perforator-plus sural neurocutaneous flap (sural flap), summarize our experience in the flap with high pivot point, and compare the outcomes between the flaps with high and low pivot points. METHODS: Five amputated lower limbs were perfused, and the integuments were radiographed. We retrospectively analyzed 378 flaps, which were divided into two groups: pivot points located ≤8.0 cm (low pivot point group) and >8.0 cm (high pivot point group) proximal to the tip of the lateral malleolus. Partial necrosis rates were compared between two groups. RESULTS: The arterial chain surrounding the sural nerve was linked by true anastomoses from the intermalleolar line to popliteal crease. True anastomoses existed among peroneal perforators and between these perforators and the arterial chain. There were 93 flaps with high pivot point and 285 flaps with low pivot point. Partial necrosis rates were 16 and 9.1% in the high and low pivot point group (p = 0.059), respectively. CONCLUSION: True anastomosis connections among peroneal perforators and the whole arterial chain around sural nerve enable the sural flap to survive with a greater length. The sural flap with high pivot point is a good option for reconstructing soft-tissue defects in the middle and distal leg, ankle, and foot, particularly when the lowest peroneal perforator presents damage, greater distance to the defects, discontinuity with the donor site, or anatomical variation.

HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer.

OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.

Dual specific CD19/CD22-targeted chimeric antigen receptor T-cell therapy for refractory diffuse large B-cell lymphoma: A case report.

Clinical trials of chimeric antigen receptors (CARs) targeting CD19 have produced impressive results in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). However, a notable number of patients with DLBCL fail to achieve remission after CD19 CAR T-cell therapy and may therefore require a dual targeted CAR T-cell therapy. A 31-year-old man with refractory DLBCL was assessed in the present case report. The patient was treated with sequential infusion of single CD19 CAR T cells followed by dual CD19/CD22-targeted CAR T cells. The outcome was that the patient achieved partial remission after the first single CD19 CAR T-cell infusion and complete remission after the dual CD19/CD22-targeted CAR T-cell infusion. Grade 1 cytokine release syndrome (CRS) was observed after the single CD19 CAR T-cell infusion, while grade 3 CRS and hemophagocytic syndrome were observed after the dual targeted CAR T-cell infusion, but these adverse effects alleviated after the treatments. To the best of our knowledge, the present case report is the first to describe the successful application of dual CD19/CD22-targeted CAR T-cell therapy for the treatment of refractory DLBCL. The report suggests that dual CD19/CD22-targeted CAR T-cell therapy may represent a promising option for the treatment of refractory DLBCL; however, caution should be taken due to potential CRS development.

Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study.

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.

Curcumin inhibits the formation of atherosclerosis in ApoE-/- mice by suppressing cytomegalovirus activity in endothelial cells.

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Long noncoding RNA TUG1 regulates the development of oral squamous cell carcinoma through sponging miR-524-5p to mediate DLX1 expression as a competitive endogenous RNA.

Long noncoding RNA (lncRNA) exerts a potential regulatory role in tumorigenesis. LncRNA TUG1 expression remains high in oral squamous cell carcinoma (OSCC) tissues. However, its biological mechanism in OSCC remains unknown. In this study, TUG1 expression in OSCC cells was detected by quantitative real-time polymerase chain reaction. Proliferative and migratory potentials of OSCC cells were determined by Cell Counting Kit 8, 5-Ethynyl-2'- deoxyuridine (EdU), and Transwell assay, respectively. We identified the potential target of TUG1 through bioinformatics and dual-luciferase reporter gene assay. Furthermore, their interaction and functions in regulating the development of OSCC were clarified by western blot and RNA immunoprecipitation assay. Our results demonstrated a high expression of TUG1 in OSCC cells. Overexpression of TUG1 markedly accelerated proliferative and migratory potentials of OSCC cells. Besides, TUG1 could positively regulate the expression of distal-less homeobox 1 (DLX1) by competing with miR-524-5p. These results indicated that TUG1 participated in the development of OSCC as a competing endogenous RNA to competitively bind to miR-524-5p and thus mediate DLX1 expression.