BackgroundSemen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro.ResultsHere, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248–286) and disrupting PAP248–286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen.ConclusionsIncorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV.Electronic supplementary materialThe online version of this article (10.1186/s12977-018-0432-3) contains supplementary material, which is available to authorized users.
Purpose: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.Methods: Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy(AT group) or chemotherapy (CT group)alone.Results: A total of 65 patients were enrolled in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy, and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival in the AT group was 11.2 months [95% confidence interval (CI), 5.9-16.5], The median progression-free survival in the CT group was 7.0 months [95%CI, 5.1-8.9][Hazard Ratio (HR), 0.49; 95%CI, 0.29-0.83; P=0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The ORR of two groups were 45.2% (95% CI, 0.27 to 0.64), 38.2% (95% CI, 0.21 to 0.56), (P = 0.571). The DCR of two groups were 93.5% (95% CI, 0.84 to 1.03), 88.2% (95% CI, 0.77 to 1.00), (P = 0.756).Conclusions: Among patients with advanced PPLELC, the progression free survival of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.
Objectives Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC), and the first-line therapy for metastatic PPLELC patients remains controversial. The purpose of this study was to investigate the efficacy and safety of immune checkpoint inhibitors(ICIs) combined with chemotherapy(CT) compared with traditional chemotherapy in these patients. Methods A total of 168 patients with metastatic PPLELC came from six grade A hospitals from August 2018 to August 2020 were selected. 17 patients were enrolled in the ICI group and received 200mg of Pembrolizumab plus albumin paclitaxel and carboplatin every 3 weeks. 34 patients with chemotherapy alone were assigned to the CT group and received albumin-paclitaxel combined with carboplatin every 3 weeks. Results As of June 1, 2021, the median PFS was 14.9 months for ICI group and 6.4 months for CT group [Hazard Ratio (HR), 0.29; 95% confidence interval (CI), 0.15-0.55; P < 0.05]. ORR was 64.7% in ICI group and 35.3% in CT group [HR, 0.65; 95%CI, 0.39-0.90; P=0.047]. The median OS of ICI group was not reached, while that of CT group was 13 months. In the ICI group, there were 8 cases (47.1%) of grade 3 treatment-related adverse reactions and 5 cases (29.4%) of grade 4 treatment-related adverse reactions. In the CT group, there were 9 cases (26.5%) of grade 3 treatment-related adverse reactions and 8 cases (23.5%) grade 4 treatment-related adverse reactions. FBXW7 mutation were negatively and TP53 mutation, MRE11A p.V198S mutation, PTEN p.T319FS mutation were positively correlated with the efficacy of immunotherapy. Conclusions In patients with metastatic PPLELC, the efficacy of immune checkpoint inhibitors combined with chemotherapy was significantly better than that of chemotherapy alone, and adverse reactions were acceptable.
Background Impaling injuries to the chest are relatively rare and often lethal. Initial evaluation, resuscitation, and surgical planning can be challenging for emergency physicians and surgeons. Chest trauma can be classified as either closed or penetrating, depending on whether or not the pleural cavity is open. Penetrating objects entering chest cavity frequently make an entrance and exit and are often accompanied by visceral/vascular damage. Open thoracotomy or video-assisted thoracic surgery (VATS) are considered the first-line approaches for severe penetrating chest trauma. Case Description A 63-year-old male patient sustained a penetrating chest trauma caused by a T-shaped metallic bar falling from a height of 16 meters above the ground. After laboratory and imaging tests, as well as pre-operative preparation, the object was pulled out from the entry site after disinfection with surgical standby. Closed chest tube drainage was promptly performed, with chest tubes inserted through the entry and exit sites. The patient was discharged on postoperative day 14 in a good condition. Regular telephone follow-ups over 3 years showed that the patient recovered well after discharge. Conclusions For penetrating non-cardiac chest trauma patients in stable condition, it is necessary to complete an exhaustive imaging evaluation to determine the specific position of the foreign body and identify any injuries to major vessels and organs. If the condition permits, direct removal of foreign bodies is allowed, ideally under VATS control. Surgeons should evaluate the best option for each case based on the available resources.
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