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Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non‐resectable (biopsy) PDACs using a next‐generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I‐II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III‐IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.

Background:Rupture of the carotid plaque is one of the main causes of cerebral embolism. The molecular mechanisms underlying carotid plaque rupture remain unknown. Many previous studies have studied the histologic instability of plaques after a stroke, but few have predicted microRNA-gene axes of plaque rupture and mapped potential target genes at the cellular level using single-cell RNA sequencing in normal and atherosclerosis samples. The aim of the present study was to systematically identity the gene signature and prediction diagnostic module, as well as hub miRNA-gene axes to explore the potential biomarkers and mechanisms associated with the carotid atherosclerosis.Results:Microarray dataset GSE163154, containing advanced atherosclerotic plaques group and early lesions group, was obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify advanced plaque-related module. Subsequently, we detected eight optimal hemorrhage-associated genes (FBLN5, FMOD, GAL, GEM, SLC14A1, STBN1, TMEM119, and GREM1) using LASSO regression analysis and confirmed by using receiver operating characteristic (ROC) curve. The area under the ROC curve was 0.951 (95% confidence interval [CI]: 0.887, 1.000) for the matched sample. The interaction of thirteen upstream microRNAs and five genes were constructed, in which microRNA-532-3p and microRNA-128 were upstream regulators of FBLN5 by searching for Starbase v3.0 and GEO datasets. Finally, through performing single-cell RNA sequencing in artery samples of 1 normal people and 1 patient with coronary atherosclerosis, we found that in atherosclerotic samples, FBLN5 was highly expressed in smooth muscle cells, derived smooth muscle cells and endotheli-al cells. Therefore, we speculated that FBLN5 mainly plays a role in atherosclerosis through being regulated by microRNA-532-3p and microRNA-128.Conclusion:This finding backs up the popular idea that miRNA-gene axis and FBLN5 are linked to acute plaque disruption and occur before symptoms appear. These genes could become targets for novel medical treatments in the future, or they could help identify patients with histologically unstable plaques who would benefit from surgical intervention if they were validated.

Background Although the rapid emergence of coronavirus disease 2019 (COVID-19) poses a considerable threat to global public health, no specific treatment is available for COVID-19. ReDuNing injection (RDN) is a traditional Chinese medicine known to exert antibacterial, antiviral, antipyretic, and anti-inflammatory effects. In addition, RDN has been recommended in the diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia by the National Health Council and the National Administration of Chinese Medicine. However, there is no information regarding its efficacy against COVID-19. Aim of study This study was designed to determine the clinical efficacy of RDN in patients with COVID-19 and characterize its antiviral activity against SARS-CoV-2 in vitro. Materials and methods A total of 50 adults with COVID-19 were included in this study, and the primary endpoint was recovery from clinical symptoms following 14 days of treatment. General improvements were defined as the disappearance of the major symptoms of infection including fever, fatigue, and cough. The secondary endpoints included the proportion of patients who achieved clinical symptom amelioration on days 7 and 10, time to clinical recovery, time to a negative nucleic acid test result, duration of hospitalization, and time to defervescence. Plaque reduction and cytopathic effect assays were also performed in vitro, and reverse-transcription quantitative PCR was performed to evaluate the expression of inflammatory cytokines (TNF-α, IP-10, MCP-1, IL-6, IFN-α, IFN-γ, IL-2 and CCL-5) during SARS-CoV-2 infection. Results The RDN group exhibited a shorter median time for the resolution of clinical symptoms (120 vs. 220 h, P, Graphical abstract Image 1

Graft remodeling after transplantation maintains graft functionality and determines graft survival. However, a comprehensive understanding of cellular diversity and interplay during graft remodeling remains to be fully characterized. In this study, we established a well tolerant C57BL/6 to C57BL/6 orthotopic liver transplantation (LT) mice model and observed two stages of graft recovery including an acute phase and a steady phase. We next performed single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) and recorded the cellular hierarchy in the transplanted liver during the two stages. Besides the dynamic change of cell proportion, it was notable that recipient-derived cells took over the transplanted liver in most cell types (e.g., B cells, T cells, dendritic cells, granulocytes and monocytes) except CD206+ MerTK+ macrophages and CD161+ CD49a+ CD49b−natural killer cells. We then focused on macrophages and captured 5 distinct transcriptional signatures to define novel subclusters. Using a ligand-receptor interaction strategy, we identified specific macrophage-hepatocyte interactions during the acute and stable phases, causing metabolic remodeling in the transplanted liver. Our results delineated a 4-dimension cell atlas (type-proportion-source-time) of the transplanted liver, which sheds light on the physiological process of liver graft maintenance and graft-recipient crosstalk.

This study was performed to evaluate the outcomes of combined bilobed trapezius myocutaneous and scapula osteomyocutaneous flaps for the restoration of through-and-through defects of the mandible. The subjects were six patients with recurrent malignant tumours who underwent salvage surgeries and reconstruction with combined flaps based on the transverse cervical vessels (TCVs). All patients had combined bone (four type H, one type LCL, and one type C) and extensive soft tissue defects (through-and-through defects) following salvage surgery. All tumours were removed and the complex defects restored successfully. Two patients experienced minor complications: one minor intraoral flap failure and one case of wound dehiscence at the donor site. The appearance of the face and neck was satisfactory or acceptable in all patients. No patient showed severely limited range of motion of the upper limb. The patients were followed up for 10 to 18months. One patient was living with no evidence of disease. The use of combined bilobed trapezius myocutaneous and scapula osteomyocutaneous flaps based on the TCVs may be an effective approach for the restoration of through-and-through defects of the mandible and may provide satisfactory or acceptable functional and aesthetic outcomes following salvage surgery for advanced head and neck tumours.

The purpose of this study was to assess the outcomes of patients with advanced recurrent nasopharyngeal carcinoma (rNPC) and radiation-induced sarcoma of the head and neck (RISHN) who underwent en bloc resection and reconstruction. Fifty-two patients with advanced rNPC (n=36) and RISHN (n=16) underwent en bloc resection and reconstruction with an extended lower vertical trapezius island myocutaneous flap (TIMF). En bloc resection of the tumour (including craniomaxillofacial resections and neck resections) and major defect restoration was successful in all patients. TIMF survival was 92.3%. Postoperative mild hemiplegia occurred in one patient with rNPC. In total, 20 patients (55.5%) in the rNPC group and seven (43.8%) in the RISHN group recovered with no signs of disease at follow-up. No statistically significant difference in recovery status was observed between the rNPC and RISHN groups. En bloc resection of the tumour, including dissection of the carotid artery, ensured microscopic clearance of the disease; this is a viable treatment option for patients with advanced rNPC or RISHN without distant metastasis. The extended vertical lower TIMF is a large, straightforward, and reliable flap for repairing the resultant major defects in the craniomaxillofacial or neck region.

Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.

Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce apoptosis in cancer cells. However, the signal pathways that can augment the proapoptotic function of ROS remain largely unknown. We previously identified a tumor suppressor, alpha-tocopherol-associated protein (TAP), yet little is known regarding the role of TAP in the apoptotic signaling in prostate cancer. Interestingly, we recently found that exposure of prostate cancer cells to hydrogen peroxide (H(2)O(2) ) resulted in induced apoptosis as well as increased expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous TAP expression conferred effective protection from H(2)O(2) -induced apoptosis. Further mechanistic study showed exposure of prostate cancer cells to H(2)O(2) resulted in increased phosphorylation of both JNK and c-Jun, and TAP siRNA effectively decreased H(2)O(2) -induced JNK and c-Jun phosphorylation. Immunoprecipitation experiments revealed that JNK physically associates with TAP. Furthermore, signaling downstream of JNK to the AP-1 complex and BH-3-only subfamily were found to be regulated on changing the TAP expression status. TAP could also promote the oxidative stress-induced apoptosis effect of docetaxel. In the mice xenograft model, H(2)O(2) treatment induced TAP expression, JNK phosphorylation and apoptosis of prostate cancer. Recombinant adeno-associated virus 2 (rAAV2)-TAP injection significantly sensitizes this H(2)O(2) proapoptotic effect. Together, we have identified a novel functional mechanism that the cross-talk of TAP-JNK is involved in oxidative stress-induced apoptosis in prostate cancer cells. Disrupting the redox balance of cancer cells by this signaling may enable therapeutic selectivity and provide benefit to overcome the drug resistance of prostate cancer.

Purpose: The purpose of this study was to develop and test a method for measuring pressure in the upper urinary tract during ureteroscopic operations and to evaluate its efficacy and clinical significance. Methods: A total of 44 patients, each with a ureteral calculus in the proximal ureteral segment, were enrolled in the study group: 21 patients with an acute and 23 with a chronic obstruction. The ureteroscope was passed forward to the upper segment of the obstructed ureter immediately after the calculus was broken and the intraluminal ureteral pressure was then transmitted along with the irrigant flow (0.9% sodium chloride). Results: The mean ureteral pressures of the acute obstruction subgroup, the chronic obstruction subgroup and the control group were 74.5 mmHg (22-180 mmHg), 32.5 mmHg (9-53 mmHg) and 10.2 mmHg (8-13 mmHg), respectively. A significant correlation was found between ureteral pressure and the following indexes: the duration of the obstruction (r=0.985), the diameter of the ureter above the calculus (r=0.878) and the depth of the hydronephrosis of the renal pelvis (r=0.862). No associations were observed between the pressure and the serum creatinine level (r=0.214) or the urinary leukocyte count (r=0.047). The intraluminal pressure correlated with the glomerular flow rate (GFR) of the affected kidney (r =0.975, P =0.001). Conclusions: This new method is non-invasive, practical and reproducible. Measuring the intraluminal pressure of the ureter can provide a valuable index to quantify the severity of the obstruction of the upper urinary tract, which is helpful for the prediction of the affected renal function prognosis.

A 63-year-old male presented with lower abdominal pain and oliguria due to a large mass in the seminal vesicles. Positron emission tomography/CT (PET/CT) examination showed multiple lesions in the seminal Vesicles, parapharyngeal space, mediastinum and spermatic cord. The result of transrectal ultrasound (TRUS)-guided biopsy indicated a diffuse, large, B-cell lymphoma of the seminal vesicles. PET-CT and TRUS guided biopsy were very helpful to make the correct diagnosis of this unique case.