[Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection].

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma.

BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.

Numerical simulation and testing of laser-MIG hybrid-welding angle-structure sheets.

Numerical simulation and experimental investigation of laser-MIG hybrid angle-welding low-carbon 1.5-mm-thin SPCC steel sheets are presented in this work. The transient simulation analysis provides an access to the thermal-fluid phenomena prediction by employing a hybrid three-dimensional heat source model. Special attention is paid to the melt dynamic behaviors within the triangular molten pool affected by the Marangoni convection. The simulation results show that the temperature and its gradient distribution are symmetrical with respect to the laser beam, which is validated well by the experimental study. The microstructure of the welded joints was analyzed by scanning electron microscopy and transmission electron microscopy. The results show that the cross-section microstructures of welded joint are mainly composed of the weld zone, narrow heat-affected zone, and substrate. The semielliptic-like molten pool shape is consistent with that of the simulated results. The finer microstructure in the weld bead results from the rapid cooling rate of laser welding confirmed by the FEM calculation. The columnar and equiaxed dendrites are formed in the peripheral and central region of the molten pool, which is beneficial for the improvement of the microhardness.

[Clinical characteristics of 11 patients with chronic lymphocytic leukemia with t (14;19) (q32;q13)].

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.

[Clinical tolerability and pharmacokinetics of troxacitabine].

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

[The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy].

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

[Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases].

OBJECTIVE: To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors. METHODS: A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging. RESULTS: (1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival. CONCLUSION: The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.

Detection of haemodynamic obstruction in hypertrophic cardiomyopathy using the sub-aortic complex: a cardiac MRI and Doppler study.

AIM: To investigate the "sub-aortic complex (SAC)", a new cardiac magnetic resonance imaging (CMRI)-derived parameter, for the evaluation of left ventricular (LV) outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM), compared with conventional CMRI parameters and Doppler echocardiography. MATERIALS AND METHODS: A total of 157 consecutive patients with HCM were recruited retrospectively. The patients were divided into two groups, 87 with LVOT obstruction and 70 without obstruction. The SAC was defined as a specific anatomical SAC affecting the LVOT, which were measured on the LV three-chamber steady-state free precession (SSFP) cine image at the end-systolic phase. The relations between the existence and severity of obstruction and SAC index (SACi) were evaluated using Pearson's correlation coefficient, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: The SACs were significantly different between the obstructive and non-obstructive groups. The ROC curves indicated that the SACi was able to discriminate obstructive and non-obstructive patients with the best predictive accuracy (AUC = 0.949, p<0.001). The SACi was an independent predictor of LVOT obstruction and there was a significant negative correlation between resting LVOT pressure gradient and SACi (r=0.72 p<0.001). In the subgroup of patients with or without severe basal septal hypertrophy, the SACi was still able to predict LVOT obstruction with excellent diagnostic accuracy (AUC = 0.944 and 0.948, p<0.001, respectively). CONCLUSION: The SAC is a reliable and straightforward CMRI marker for assessing LVOT obstruction. It is more effective than CMRI two-dimensional flow in diagnosing the severity of obstruction in patients with HCM.

[Clinical analysis of laparoscopic treatment of chronic traumatic diaphragmatic hernia in 29 cases].

Objective: To examine the safety and effectiveness of laparoscopic individualized surgical treatment for chronic traumatic diaphragmatic hernia (CTDH). Methods: The clinical data and follow-up data of 29 CTDH cases admitted to the Qilu Hospital of Shandong University or the First Affiliated Hospital of Shandong First Medical University from June 2015 to January 2023 were retrospectively analyzed. There were 21 males and 8 females, aged (49.4±17.8) years (range: 19 to 79 years). The main clinical manifestations were symptoms of the digestive system and respiratory system, and only 4 cases were asymptomatic. All patients received laparoscopic treatment (conversion to open surgery was not excluded). Intraoperative exploration (location of the hernia, contents of the hernia, diameter of the hernia ring), surgical conditions (surgical repair plan, operation time, blood loss, postoperative complications) and postoperative follow-up were analyzed and discussed. Results: Laparoscopic repair was successfully completed in 27 cases, including simple suture in 6 cases, suture and patch repair in 17 cases, the anterior abdominal wall muscle flap reversal suture and patch repair of in 3 cases, and patch bridge repair in 1 case. The operation time was (112.8±44.7) minutes (range: 60 to 200 minutes). The amount of bleeding (M(IQR)) was 35 (58) ml (range: 10 to 300 ml). The other 2 patients were converted to laparotomy. Except for one patient with transverse colon strangulation necrosis who died of aggravated pulmonary infection after surgery, the remaining 28 patients were discharged successfully. The follow-up time was 36 (24) months (range: 1 to 60 months). During the follow-up period, only two patients had occasional left upper abdominal discomfort. Twenty-seven patients with left diaphragmatic hernia had no recurrence, and the symptoms of 1 patient with right diaphragmatic hernia were relieved. Conclusion: Customized laparoscopic surgical repair for CTDH according to the location and size of the diaphragmatic defect can achieve good surgical results.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

Effects of powder size and preset thickness on the microstructure and properties of Ni35 thin coating prepared by laser cladding.

Ni35 thin coatings were prepared on 40Cr steel by preset powder laser cladding technology. The effects of powder size and preset thickness on the dilution rate, microstructure, and properties of the coating were systematically studied. The results showed that the coating with smaller powder size and larger preset thickness had smaller grain size, denser microstructure, a flatter bottom of the molten pool, and lower dilution rate. The micro-hardness of the coating with large powder size and preset thickness was higher. The friction coefficient of the coating with small powder size and small preset thickness was smaller, but the latter had larger curve fluctuation and wear volume loss. The corrosion rate of the coating was high during the first 24 h, then relatively stable after 68 h, and the corrosion rate and loss of the coating with small powder size and large preset thickness were smaller.

Comparison between use of direct oral anticoagulants and aspirin for risk of thromboembolism complications in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Total knee and hip arthroplasty are one of the most commonly consistently successful surgeries in orthopedics worldwide. Literature has reported that depending upon the age and co-existing treatments, patients undergoing total knee and hip arthroplasty are often prone to increased risks of developing venous thromboembolic complications. In such cases, chemoprophylaxis with either direct oral anticoagulant therapy with factor-Xa inhibitors (i.e., rivaroxaban, apixaban, dabigatran) and aspirin are widely recommended. Recent surveys suggest that direct oral anticoagulants and aspirin have comparable efficacy. However, there is no consensus in the literature as to which drug is the safest. Therefore, in this review, we shall attempt to evaluate the comparative efficacy between direct oral anticoagulant drugs and aspirin in patients undergoing total joint arthroplasty. To compare risk of venous thromboembolism complications between use of direct oral anticoagulant drugs and aspirin in patients undergoing total knee and hip arthroplasty. MATERIALS AND METHODS: A sensitive and specific analysis of the literature was performed according to the Cochrane and written according to PRISMA guidelines (Supplementary Table I). Five electronic databases (Web of Science, Embase, CENTRAL, Scopus, and Medline) were evaluated. To compare the efficacy between the drugs we conducted a random-effect meta-analysis according to the outcome (bleeding complications, venous thromboembolism or pulmonary embolism) and overall mortality in patients undergoing total knee and hip arthroplasty. RESULTS: Overall, 993 studies were found of which 117 had their full texts evaluated. A total of 161,463 patients undergoing total joint arthroplasty with mean age equal 66.2 ± 5.0 years were identified in 14 studies. Higher risks of venous thromboembolism (OR: 1.56 95% CI 1.21-2.01), pulmonary embolism (OR: 1.63, 95% CI: 1.31 -2.04) and overall mortality (OR: 1.35, 95% CI 1.04-1.74) for patients receiving aspirin were verified as compared to direct oral anticoagulant drugs. Subsequently, we further observed that the risks of bleeding complications (OR: 0.89 95% CI 0.67-1.18) were insignificant. CONCLUSIONS: The study reports higher risks of venous thromboembolism, pulmonary embolism, and overall mortality for the patients receiving aspirin before undergoing.

Does prior arthroscopic procedure impact outcomes of knee arthroplasty? A systematic review and meta-analysis.

OBJECTIVE: Despite generally favorable outcomes following knee arthroscopy, a certain subset of patients inevitably develops progression of knee disease, necessitating subsequent total knee arthroplasty (TKA). Therefore, the evaluation of TKA outcomes following arthroscopy has emerged as a major area of research. The aim of the current review is to measure the impact of prior arthroscopy on functional and adverse outcomes following TKA. MATERIALS AND METHODS: Literature search was conducted in the databases including Medline, EMBASE, PubMed Central, ScienceDirect, Google Scholar and Cochrane library from inception until April 2021. Meta-analysis with random-effects model was conducted to calculate pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. RESULTS: In total, 9 studies with 185,013 participants were included in the review. The majority of the studies were conducted in the USA and China. Almost all the studies had low quality as per Newcastle Ottawa (NO) scale. The pooled SMD for functional outcome was -0.19 [95%CI: -0.30 to -0.09], while the pooled OR for revision rate was 1.53 (95% CI: 1.21 to 1.92). In terms of postoperative complications, the pooled OR for stiffness was 1.55 (95% CI: 0.92-2.61), infection was 1.39 (95%CI: 1.17-1.67), aseptic loosening was 1.93 (95% CI: 1.19-3.11), VTE was 1.06 (95% CI: 0.83-1.35), and MUA was 1.33 (95% CI: 1.13-1.57) respectively. CONCLUSIONS: Prior arthroscopy has significant impact on the functional and adverse clinical outcomes following TKA. Surgeons need to develop a comprehensive intervention plan to manage these high-risk patients and reduce the rate of postoperative complications.

[Surgical treatment of Stanford type A aortic dissection after thoracic endovascular aortic repair].

Objective: To examine the surgical treatment of Stanford type A aortic dissection (type A dissection) after thoracic endovascular aortic repair (TEVAR). Methods: The data of 58 patients with reoccurrence of type A dissection after TEVAR admitted into the Department of Cardiovascular Surgery, Henan Chest Hospital from February 2012 to January 2020 were analyzed retrospectively. There were 40 males and 18 females, aged (57.0±6.7) years (range: 31 to 71 years). The time between recurrence of type A dissection and TEVAR (M(QR)) was 37 days (72.8 months) (range: 1 h to 14 years). Forty-eight cases underwent emergency operation, 9 cases underwent sub-emergency operation, and 1 case died of dissection rupture on the way to the operating room. All 57 patients underwent radical treatment. Fifty-four cases underwent the frozen elephant trunk technique under deep hypothermia circulatory arrest and selective cerebral perfusion, and 3 cases (>65 years old) underwent arch debranch anastomosis+ascending aorta replacement+descending arch covered stent implantation under mild hypothermia. Results: The operation time was (445±32) minutes (range: 382 to 485 minutes), the aortic crossclamp time was (103±19) minutes (range: 89 to 133 minutes), the cardiopulmonary bypass time was (189±27) minutes (range: 162 to 221 minutes), and the intraoperative blood loss was (665±343) ml (range: 450 to 1 750 ml). Postoperative ICU stay time was 5 (6) days (range: 2 to 27 days), and postoperative hospital stay was 14.0 (4.5) days (range: 2 to 36 days). Three cases died, including 2 cases with severe brain complications and 1 case with systemic multiple organ failure caused by severe liver insufficiency and gastrointestinal hemorrhage. Postoperative follow-up was 0.5 to 7.0 years, which showed that 1 case had left coronary artery anastomotic stoma fistula 3 months after operation and underwent reoperation, 2 cases underwent thoracoabdominal aortic replacement again, and the rest of patients had no anastomotic stoma fistula and incomplete stent distortion and expansion on CT angiography. Four cases died during follow-up, and 1 case died of sudden cerebral infarction 2 years after operation. Conclusion: The recurrent type A dissection after TEVAR is mostly related to stent graft, and the patients can undergo operation actively with good prognosis.

Breast ductal carcinoma in situ with micro-invasion versus ductal carcinoma in situ: a comparative analysis of clinicopathological and mammographic findings.

AIM: To determine the differences in clinicopathological and mammographic findings between ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with micro-invasion (DCIS-MI) and explore clinicopathological and mammographic factors associated with DCIS-MI. MATERIALS AND METHODS: All DCIS patients with or without micro-invasion who underwent preoperative mammography at The Affiliated Hospital of Qingdao University from January 2016 through June 2020 were identified retrospectively. The correlations of clinicopathological findings with DCIS-MI were evaluated using univariate and multivariate binary logistic regression analyses. Imaging findings were compared between the groups by using the Pearson chi-square test. RESULTS: A total of 445 DCIS lesions and 151 DCIS-MI lesions were included in the final analysis. Large extent (≥2.7 cm), high nuclear grade, comedo-type, negative progesterone receptor (PR), negative oestrogen receptor (ER), high Ki-67 and axillary lymph node metastasis were more frequently found in DCIS-MI than in DCIS (all p<0.05), and the first four of these were found to be independent predictors of DCIS-MI in the multivariate analysis (all p<0.05). Regarding imaging findings, compared to DCIS, DCIS-MI showed fewer occult lesions and more lesions with calcifications in mass, asymmetry, and architectural distortion (p=0.004). Grouped calcifications were usually associated with DCIS, while regional calcifications were commonly found in DCIS-MI (p<0.05). CONCLUSION: Large extent, high nuclear grade, comedo-type and negative PR were found to be independent predictors of DCIS-MI. Lesions with calcifications and regional calcifications were more likely associated with DCIS-MI on mammography.

Impact of biologic disease-modifying antirheumatic drugs on fracture risk in patients with rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to assess the impact of biologic disease-modifying antirheumatic drugs (bDMARDs) use on the risk of fracture in rheumatoid arthritis (RA) by conducting a pooled analysis of adjusted outcomes from individual studies. MATERIALS AND METHODS: PubMed, Embase, and BioMed Central were searched up to 20th January 2021. Multivariable-adjusted odds ratios (OR) or matched estimates on the impact of bDMARDs on fracture risk were pooled. RESULTS: Nine studies were included. We found no statistically significant difference in the risk of fractures in RA patients using bDMARDs vs. non-users. On sensitivity analysis, we found no change in the significance of the effect size on exclusion of any study. There was no statistically significant difference in fracture risk in studies only on tumor necrosis factor (TNF) inhibitors, as well as those including any bDMARDs. Pooled analysis of only three studies indicated a statistically significant reduction in vertebral fractures in bDMARD users vs. non-users. CONCLUSIONS: Within the ambit of several limitations of our review, there seems to be no impact of bDMARDs on the fracture risk in RA patients. Further studies evaluating the type and duration of bDMARD therapy with meticulous adjustment of confounding factors are required to strengthen current evidence.

Characterization of TCR+ and CD8+ head kidney leucocytes in Japanese flounder (Paralichthys olivaceus) with antisera against TCRα and CD8α.

T lymphocytes play an important role in cellular and adaptive immunity in vertebrates. The mechanisms of the fish immune system are little studied because of the lack of population-specific antibodies. This study examined the expression of two T lymphocyte markers, TCRα (PoTCRα) and CD8α (PoCD8α) in the Japanese flounder (Paralichthys olivaceus). The expression of PoTCRα and PoCD8α was mainly detected in immune/mucosal tissues. Recombinant PoTCRα and PoCD8α were expressed in pET32a and pET259, respectively. Then, rabbit anti-PoTCRα serum and rat anti-PoCD8α serum were prepared. Using serum, the characteristics of TCR+ and CD8+ head kidney leucocytes (HKLs) were investigated. The results of laser scanning confocal microscopy (LSCM) demonstrated that TCRα and CD8α were transmembrane proteins localized on the cell surface. The populations of CD8α- , CD8α+ , TCRα- , and TCRα+ were sorted by flow cytometry (FCM) and analysed using qRT-PCR. The results demonstrated that all TCRα+ /TCRα- or CD8α+ /CD8α- HKLs expressed IFN-γ. The CD4-1 and IgM transcripts were detected only in TCRα- and CD8α- cells. Furthermore, HKL mitogenesis was induced with concanavalin A (ConA) stimulation. Taken together, the results from LSCM and FCM analyses showed that mammalian and P. olivaceus TCR+ and CD8+ leucocytes share basic characteristics.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.