Association of plasma sPD-1 and sPD-L1 with disease status and future relapse in AQP4-IgG (+) NMOSD.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated disorder with aquaporin 4-immunoglobulin G (AQP4-IgG) in most settings. Soluble programmed death-1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) play key roles in immunomodulation. We aim to assess the association of sPD-1 and sPD-L1 with cytokines and their clinical significance in AQP4-IgG (+) NMOSD. METHOD: We measured plasma sPD-1, sPD-L1, and 10 cytokines levels of 66 AQP4-IgG (+) NMOSD patients, including 40 patients in attack (attack-NMOSD) and 26 patients in remission (remission-NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP-X platform, respectively. We also performed >2 years (median) of follow-up after testing and analyzed the relationship between the detection index and current and future clinical parameters. RESULT: Plasma sPD-1 level discriminated attack-NMOSD from remission-NMOSD (AUC = 0.692, p = 0.009). sPD-1 and sPD-L1 levels positively correlated with IL-6 (rsPD-1 = 0.313; rsPD-L1 = 0.508), IFN-γ (rsPD-1 = 0.331; rsPD-L1 = 0.456), and TNF-α (rsPD-1 = 0.451; rsPD-L1 = 0.531) expression, as well as clinical indicators, including the EDSS score (rsPD-1 = 0.331; rsPD-L1 = 0.402), number of attacks (rsPD-1 = 0.431) and segments of spinal cord involvement (rsPD-1 = 0.462; rsPD-L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD-1/sPD-L1 ratio in attack-NMOSD (p = 0.022; Exp(B) = 1.589). INTERPRETATION: Plasma sPD-1 and sPD-L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4-IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment.

Synergistic Fermentation with Functional Microorganisms Improves Safety and Quality of Traditional Chinese Fermented Foods.

Traditional fermented foods are favored by people around the world for their positive health and taste advantages. Many of the fermented foods, including Chinese traditional fermented foods, are produced through mixed-culture fermentation. Apart from reducing the formation of harmful compounds such as ethyl carbamate (EC) and biogenic amines (BAs) during food fermentation, it is also difficult to precisely control and regulate the fermentation process based on the control of environmental conditions alone, due to the complex microbiota and an unclarified fermentation mechanism. In this review, key microorganisms involved in Chinese fermented foods such as baijiu, soy sauce, and vinegar production are elaborated, and relations between microbial composition and the aroma or quality of food are discussed. This review focuses on the interpretation of functions and roles of beneficial (functional) microorganisms that participate in food fermentation and the discussion of the possibilities of the synergistic use of functional microorganisms to improve the safety and quality of Chinese fermented foods. Conducting work toward the isolation of beneficial microorganisms is a challenge for modern food fermentation technology. Thus, methods for the isolation and mutagenesis of functional microbial strains for synergistic food fermentation are summarized. Finally, the limitations and future prospects of the use of functional microorganisms in traditional Chinese fermented foods are reviewed. This review provides an overview of the applications of synergistic fermentation with functional microorganisms in the improvement of the safety or sensory qualities of fermented foods.

Effect of Different Durations of Adjuvant Capecitabine Monotherapy on the Outcome of High-Risk Stage II and Stage III Colorectal Cancer: A Retrospective Study Based on a CRC Database.

(1) Background: The duration of adjuvant chemotherapy recommended by the NCCN guidelines is 6 months. However, patients are not compliant with intravenous chemotherapy for many reasons; therefore, one approach is to obtain a survival benefit by prolonging the duration of capecitabine monotherapy. (2) Methods: A total of 355 qualified colorectal cancer (CRC) patients from January 2010 to December 2020 at West China Hospital of Sichuan University were selected to receive capecitabine monotherapy for 6−9 months and >12 months. The main endpoints were overall survival (OS) and disease-free survival (DFS). (3) Results: Among stage III patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 80.7%% and 66.8%, respectively, and the 5-year OS rates were 94.7%% and 88.8%, respectively. Among high-risk stage II patients, in the >12 months (12M) and 6−9 months (6M) groups, the 5-year DFS rates were 81.5% and 78.6%, respectively, and the 5-year OS rates were 93.1% and 84.2%, respectively. (4) Conclusions: Twelve months of chemotherapy demonstrated superior OS and DFS to that of six months in the stage III group but showed no difference in the high-risk stage II group. The better OS and DFS observed in the 12-month treatment period could be of value in selected cases.

Chemotaxis of Clostridium Strains Isolated from Pit Mud and Its Application in Baijiu Fermentation.

Clostridium is the key bacteria that inhabits the pit mud in a fermentation cell, for the production of strong-flavor Baijiu. Its activities in the process of Baijiu fermentation is closely related to the niches of pit mud and cells. After multiple rounds of underground fermentation, Clostridium has been domesticated and adapted to the environment. The mechanisms of clostridia succession in the pit mud and how they metabolize nutrients present in grains are not clear. In this study, 15 Clostridium species including three firstly reported ones (Clostridium tertium, Clostridium pabulibutyricum and Clostridium intestinale) in strong-flavor Baijiu pit mud, were isolated from the pit mud. Eighty one percent of these Clostridium strains are motile, and most of them show chemotaxis to organic acids, glutathione, saccharides and lactic acid bacteria. In a simulated Baijiu fermentation system, Clostridium migrated from pit mud to fermented grains with the addition of chemokine lactic acid, resulting in the production of acetic acid and butyric acid. The results help to understand the succession mechanism of Clostridium in pit mud, and provide a reference for regulation of lactic acid level in fermented grains during Baijiu fermentation.

Gut microbes enlarged the protective effect of transplanted regulatory B cells on rejection of cardiac allografts.

BACKGROUND: Regulatory B cells (Bregs) play an important role in maintaining immune homeostasis and have the potential to induce tolerance. Previous work has found that Breg cells are involved in heart transplantation tolerance. However, the effect of Breg on the transplantation tolerance and the underlying mechanisms remain to be clarified. METHODS: Using a within-species heart transplantation model, we aimed to investigate the role of CD19+CD5+CD1dhigh Bregs isolated from transplanted mice in preventing transplant rejection in vivo. We also explored the effects of CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitin ligase on Breg-mediated prolongation of survival in heart transplant (HT) mice, and the regulatory effects of downstream Cdk4 and Cdk6 proteins on dendritic cells (DCs), which clarified the function and molecular mechanism of Breg cells in HT mice. RESULTS: Our data suggest that adoptive transfer of the transplanted Bregs served as an effective tolerance-inducing mechanism in HT mice and was involved in the CD40-TRAF6 signaling pathway in DCs. Moreover, DCs collected from the Breg treated HT mice also prolonged the survival of HT mice. Furthermore, DC-specific knockout of TRAF6 diminished Breg-mediated prolongation of survival in HT mice. Interestingly, gut microbes from donors increased the survival of cardiac allografts both in both the absence and presence of Bregs but were not implicated in CD40-TRAF6 signaling. CONCLUSIONS: These findings reveal a role of Breg cells in the induction of transplantation tolerance through the blockade of the CD40-TRAF6 signaling pathway, which might be used in the treatment of HT in the clinic.

Diagnostic mystery-a rare right ventricular cardiac hemangioma: a case report.

BACKGROUND: Cardiac hemangiomas are rare in all kinds of benign cardiac tumors. Although cardiac hemangiomas affect all ages and may occur anywhere within the heart, right ventricular hemangiomas are extremely uncommon. CASE PRESENTATION: We report a 56-year-old woman presented with chest tightness and breath shortness for 3 months. Transthoracic echocardiography and coronary computed tomography angiography showed a mass located adjacent to the apex of the right ventricle but both failed to figure out where the mass originated from, remaining a diagnostic mystery preoperatively. The mass was removed successfully and the histopathological examination confirmed it was hemangioma. CONCLUSIONS: Cardiac magnetic resonance should be the ultimate diagnostic tool of cardiac tumors. Surgical removal, associated with a low recurrence rate and long-term survival benefits, should be the first choice of therapy for cardiac hemangiomas.

A graft inversion technique for retrograde type A aortic dissection after thoracic endovascular repair for type B aortic dissection.

BACKGROUND: Retrograde type A aortic dissection (RTAD) is a rare but life-threatening complication after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). A graft inversion technique was applied to distal anastomosis in total arch replacement for this complicated dissection. We reviewed our results of the processing for this serious complication. The aim is to evaluate the feasibility of this technology. METHODS: From January 2013 to December 2017, 20 patients (80% male, mean age 50.9 ± 9.5 years) with retrograde type A aortic dissection after thoracic endovascular aortic repair for type B aortic dissection were scheduled for surgical treatment at our center. All patients underwent an ascending aorta and total aortic arch replacement procedure. The 20 patients were divided into two groups, 1 group involved 9 patients underwent surgery using stepwise technique; the graft inversion technique was performed in the other group containing the remaining 11 patients. The postoperative variables, including cardiopulmonary bypass time, the circulatory arrest time, the aortic cross clamp time, were analyzed. Meanwhile we also analyzed the postoperative mortality and complications to evaluate the early and mid-term outcomes of surgical treatment for RTAD after TEVAR. RESULTS: In-hospital mortality was 10% (2 of 20 patients). No patient developed postoperative paraplegia, renal failure, stroke, or distal anastomotic bleeding. Two patients developed renal insufficiency, one developed neurologic insufficiency, and one developed pulmonary infection, all of which were managed accordingly. Cardiopulmonary bypass (CPB) time, and circulatory arrest time were significantly shorter in the graft inversion group than in the stepwise group (165.8 ± 37.9 min versus 206.1 ± 46.8 min, p<0.05; 34.5 ± 5.6 min versus 42.4 ± 9.5 min, p<0.05, respectively). The 18 survivors had a mean follow-up of 25.8 ± 18.2 months, and all patients remained alive and well. CONCLUSION: Graft inversion can enable a secure distal anastomosis under good surgical exposure, resulting in reduced durations of CPB, and circulatory arrest for RTAD after TEVAR. Surgical treatment could be a safe alternative for treatment of this patients.

microRNA-148a-3p inhibited the proliferation and epithelial-mesenchymal transition progression of non-small-cell lung cancer via modulating Ras/MAPK/Erk signaling.

Son of sevenless (SOS) is one of the guanine nucleotide exchange factors that can regulate the mitogen-activated protein kinase/extracellular signal regulated kinase signal pathway via controlling the activation of Ras. microRNAs are key regulon of gene expression and would be treated as tumor biomarkers or therapeutic targets. In this study, we find that miR-148a-3p acts as a tumor-suppressor in the development and progression of non-small-cell lung cancer (NSCLC). miR-148a-3p inhibits NSCLC cells proliferation and epithelial-mesenchymal transition by reducing the expression of SOS2, which refers Ras activating. Our findings demonstrate that the miR-148a-3p may play a significant role in NSCLC including the kind of lung cancer with K-Ras gene mutation, and it exerted the tumor inhibitor function by targeting SOS2. Because of that, miR-148a-3p and SOS2 may be an efficient target in developing more useful therapies against NSCLC.

A rare case report of early bioprosthetic valve thrombosis presenting with acute heart failure salvaged by thrombectomy.

BACKGROUND: Bioprosthetic valve thrombosis is previously considered as an extremely rare complication which hasn't been systemically recognized and understood. CASE PRESENTATION: Herein, we present an unusual case of a patient manifesting with acute heart failure, secondary to thrombus formation in a porcine aortic bioprosthesis which was implanted 11 months prior to hospitalization. Due to the patient's poor heart function and intraoperative findings, thrombectomy was performed. For our best knowledge, cases of early bioprosthetic valve thrombosis presenting with acute heart failure have seldomly been reported. CONCLUSION: Our study reviews predisposing factors, typical echocardiographic features and treatment for bioprosthetic valve thrombosis and it should be considered as a reason for bioprosthetic malfunction. A combination of clinical and echocardiographic features can help for diagnosis preoperatively. In some certain circumstances, early reoperation can be avoided if anticoagulant therapy works.

Notch1 is associated with the differentiation of human bone marrow­derived mesenchymal stem cells to cardiomyocytes.

Notch signaling is involved in the early process of differentiation to determine the fate of stem cells. However, the precise role of Notch in human bone marrow­derived mesenchymal stem cells (hBMSCs) remains unclear. The present study aimed to investigate the involvement of Notch signalling during the course of hBMSC differentiation into cardiomyocytes using hBMSCs, with multilineage differentiation ability, isolated and purified from human bone marrow. Flow cytometric analysis revealed that CD29, CD44 and CD90 were highly expressed on the surface of cells in their fifth passage, whereas detection of CD34, CD45, CD54 and HLA­DR was negative. Visualization of morphological changes, western blotting, immunocytochemistry and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) demonstrated that hBMSCs differentiate into cardiomyocytes through treatment with 5­azacytidine (5­aza). Transmission electron microscopy revealed ultramicroscopic details of differentiated hBMSCs. Western blotting and immunocytochemistry demonstrated increased protein expression levels of α­actin and cardiac troponin T expression, and RT­qPCR revealed increased mRNA expression of Notch1 early in the process of differentiation (days 1, 4 and 7), and increased mRNA expression levels of the transcription factors GATA binding protein­4 and NK2 homeobox 5 at day 28 day. In conclusion, differentiation of hBMSCs into cardiomyocytes was induced in vitro by 5­aza, and was associated with upregulation of Notch1, GATA binding protein­4 and Nkx2.5 expression. Overexpression of the Notch1 signaling pathway may represent a potential mechanism underlying the differentiation of hBMSCs.

Collagen scaffolds combined with collagen-binding ciliary neurotrophic factor facilitate facial nerve repair in mini-pigs.

The preclinical studies using animal models play a very important role in the evaluation of facial nerve regeneration. Good models need to recapitulate the distance and time for axons to regenerate in humans. Compared with the most used rodent animals, the structure of facial nerve in mini-pigs shares more similarities with humans in microanatomy. To evaluate the feasibility of repairing facial nerve defects by collagen scaffolds combined with ciliary neurotrophic factor (CNTF), 10-mm-long gaps were made in the buccal branch of mini-pigs' facial nerve. Three months after surgery, electrophysiological assessment and histological examination were performed to evaluate facial nerve regeneration. Immunohistochemistry and transmission electron microscope observation showed that collagen scaffolds with collagen binding (CBD)-CNTF could promote better axon regeneration, Schwann cell migration, and remyelination at the site of implant device than using scaffolds alone. Electrophysiological assessment also showed higher recovery rate in the CNTF group. In summary, combination of collagen scaffolds and CBD-CNTF showed promising effects on facial nerve regeneration in mini-pig models.

Post-traumatic coronary occlusion and left ventricular aneurysm.

Left ventricular aneurysm is a rare complication of blunt chest trauma. We now report a case of left ventricular aneurysm following blunt chest trauma associated with an acute coronary occlusion.

Resection of an invasive thymoma extending into the superior vena cava and right atrium.

Although invasive thymoma commonly infiltrates mediastinal structures, intracardiac extension from intracaval growth is rare. We present a case of invasive thymoma with intravascular invasion of the superior vena cava extending into the right atrium.