Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling.

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14-CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature ("cluster 6") that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

Small-Molecule Antagonist Targeting Exportin-1 via Rational Structure-Based Discovery.

Exportin-1 (also named as CRM1) plays a prominent role in autoimmune disorders and has emerged as a potential therapeutic target for colitis. Here we report on the rational structure-based discovery of a small-molecule antagonist of exportin-1, LFS-829, with low-range nanomolar activities. The co-crystallographic structure, surface plasmon resonance binding assay, and cell-based phenotypic nuclear export functional assay validated that exportin-1 is a key target of LFS-829. Moreover, we demonstrated that the C528S mutation or the knockdown on exportin-1 can abolish the cellular activities of LFS-829. Strikingly, oral administration of LFS-829 can significantly reverse the pathological features of colitis model mice. We revealed that LFS-829 can attenuate dual NF-κB signaling and the Nrf2 cytoprotection pathway via targeting exportin-1 in colitis mice. Moreover, LFS-829 has a very low risk of cardiotoxicity and acute toxicity. Therefore, LFS-829 holds great promise for the treatment of colitis and may warrant translation for use in clinical trials.

[Endoscopic transnasal approach for nasopharyngeal angiofibroma without arterial embolism].

OBJECTIVE: To explore the feasibility of endoscopic resection without arterial embolism for nasopharyngeal angiofibroma and the strategy of decreasing the bleeding during the operation. METHODS: The clinical data of twenty-five cases of nasopharyngeal angiofibroma were retrospective analyzed, including 3 cases of Radowski stageIIa, 5 cases of stageIIb, 4 cases of stageIIc and with 13 cases of stage IIIa. All cases did not receive the arterial embolism, and controlled hypotension were adopted under endoscopic transnasal approach during the tumor resection. Two cases were added the labiogingival incision. During the operation, under the opening vision, cutting out the outside of the infratemporal fossa, and the pterygoid process to adequate exposure the pterygopalatine fossa and infratemporal fossa.Early recognition of anatomical landmarks and establish the safety plane, along the periphery of the tumor to proceed with micro-separation, early blocking tumor nutrient vessels, en bloc resection of the tumor and some other ways to reduce bleeding and tumor resection. RESULTS: Amount of bleeding during operation was 600-1500 ml, none of them had internal carotid artery injury and intracranial injury or some other complication.Follow-up 2-3 years was available in all patients, except 1 case with residual of tumor surrounding the optic nerve, the other 24 cases had no residual tumor and relapses. CONCLUSIONS: The preoperative occlusion and artery ligation may not be needed.Surgical technique is the key to reduce blood loss, and it is feasible to have endoscopic resection of nasopharyngeal angiofibroma with proper operating technique.

[Clinical analysis of diagnosis and treatment on retro-esophageal space abscess].

OBJECTIVE: To explore the clinical manifestations and treatments of retro-esophageal space abscess. METHOD: The clinical data of 27 cases with retro-esophageal space abscess were analyzed retrospectively. Twenty-one cases (77. 78%) were secondary to acute injury of esophageal meatus caused by foreign bodies. 2 cases (7. 41%)were secondary to old foreign body infection in retro-esophageal space, 3 cases (11. 11%) after secondary to pharyngeal abscess, and 1 case (3. 70%) was unknown to etiology. All patients were confirmed by sectional medicalimageology. Six cases(Conservation group, C group) were treated conservatively and 6 cases (Oropharyngeal incision group, OI group) were performed with oropharyngeal incision drainage. 15 cases(Extra-neck incision group, ENI group)were performed with extra-neck incision and vacuum sealing drainage. RESULT: In C group, 6 cases were cured with conservative therapy and the average hospital stay was 15. 6 days. In OI group, 5 cases were healed with oropharyngeal drainage but aspiration pneumonia complicated with septic shock occurred in 2 cases, and 1 case dead from septic shock secondary to mediastinum and lung abscess. The average hospital stay was 18. 8 days. In ENI group, 15 patients were cured with extra-neck drainage without complication and the average hospital stay was 9. 5 days. CONCLUSION: The main causes of retro-esophageal space abscess are foreign body injury of upper esophagus and remnant of retro-esophageal space. Sectional medicalimageology can be of important value of diagnosis and treatment for displaying the retro-esophageal space abscess and other deep cervical fascia space sufficiently. Incision and vacuum sealing drainage via extra-neck is an effective therapy while oropharyngeal drainage is less effective and is not advocated as a primary treatment because of aspiration pneumonia complication . Conservative cure is a choice for patients without dyspnoea and background diseases, and it is necessary to recognize and treat severe complications early.

[The clinical analysis and treatment of facial paralysis caused by temporal bone tumors].

OBJECTIVE: To explore the clinical features, pathologic characteristics and treatments of the facial paralysis caused by temporal bone tumors. METHOD: Retrospective analyzed the 23 clinical data of peripheral facial paralysis caused by temporal bone tumors, including 11 cases of facial nerve tumor: facial nerve neurilemmoma in 8 cases, facial nerve neurofibroma in 3 cases; 12 cases of temporal bone malignant tumor: temporal bone squamous cell carcinoma in 9 cases, chondrosarcoma in 1 case, rhabdomyosarcoma in 2 cases. All the patients accepted the CT scan examination and MRI examination. Twenty-three cases were surgically treated: facial nerve tumor resection were performed in 11 cases, among those, through mastoid approach in 7 cases, combined mastoid with middle cranial fossa approach in 3 cases, combined mastoid with parotid approach in 2 cases. Eight cases underwent facial nerve graft following the surgical removal of tumors. Twelve cases were temporal bone malignant tumor resection: among those, extended mastoidotympanectomy in 5 cases, subtotal temporal bone resection in 6 cases, total temporal bone resection in 1 case, all were treated by radiotherapies after surgeries. RESULT: Whether the tumors go along the facial nerve in imaging is the major identification method to identify the facial nerve tumors or no-facial nerve tumors. During the 3-8 years follow-up, 10 patients who were totally removed the facial nerve tumor were no recurrence, 1 patient had tumors present. The recurrence rate of temporal bone malignancy was 41. 7% (5/12), 5 cases of Stell stage T2 and 5 cases of stage T3. The 5-year survival rate was 66.7% (8/12). CONCLUSION: Most of facial nerve tumors that cause the facial palsy are benign, and no-facial nerve tumors are most common among the malignant tumors. CT and MRI films are valuable for the diagnosis. Operation is the major treatment, the manner of the operation bases on the type and the extent of the tumors. Facial nerve grafting can improve the facial neurological function after the tumor excision. Malignancy should be treated by combination of operation and radiotherapy, etc.

[Trans-sphenoid sinus-clivus endoscopic management of petrous apex cholesterol granuloma].

OBJECTIVE: To explore the endoscopic management of petrous apex cholesterol granuloma through trans-sphenoid sinus-clivus approach. METHOD: One case of right-side petrous apex cholesterol granuloma were undertaken surgical treatment through trans-sphenoid sinus-clivus approach, then the possibility of any other approach and their advantages and disadvantages were analyzed. RESULT: The operation was success without any complications. Patient's hearing was recovered and tinnitus vanished. The patient was discharge from hospital at the third day after operation, and followed up for four month without recurrence. CONCLUSION: Trans-sphenoid sinus clivus endoscopic management of petrous apex cholesterol granuloma is effective and safe. The operators can monitor internal carotid artery then to access to the diseased region with reducing risk.

[Nasal endoscopic surgical treatment for chondrosarcoma of paranasal sinus and the skull base].

OBJECTIVE: To discuss the clinical characteristics and treatments for chondrosarcoma of paranasal sinus and the skull base. METHODS: The clinical characteristics of chondrosarcoma of paranasal sinus and skull base in 7 patients underwent endoscopic surgeries between 2001 and 2008 were analyzed. Of the patients, 4 men and 3 women. The patients' age ranged from 18 to 47 years, with a median of 31 years. CLINICAL SYMPTOMS: stuffy, nose bleeding, runny, headache, diplopia, eye outreach limited, blurred vision and even blindness. Surgery methods: under nasal endoscopy, after the attachment sites of the tumors to normal tissues were confirmed, the tumors were peeled off along the clear boundary between the tumors and normal tissues, and the potential residual tumor tissues on bones were cleared by a drill. RESULTS: The patients were followed up postoperatively for 24 to 108 months, with a median of 36 months. Five of 7 patients were no recurrence, 2 were alive with tumor. CONCLUSIONS: Chondrosarcoma of paranasal sinus and skull base can be treated by nasal endoscopic surgery, with good clinical outcome.

[Genetic diversity of ancient tea gardens and tableland tea gardens from Yunnan Province as revealed by AFLP marker].

This study was conducted to evaluate the genetic diversity within and among the plants of four ancient tea gardens and two tableland tea gardens form Yunnan Province, China by AFLP technique. The percentage of polymorphic loci (P) of the plants from six tea gardens was 92.31%. The genetic diversity within the six gardens demonstrated by Nei cents genetic diversity (He) was estimated to be 0.1366, while Shannon indices (Ho) were 0.2323. The percentage of polymorphic loci of the four ancient tea populations was 45.55% on average, with a range of 36.44% (Mengsong) to 59.11% (Mengla). But the percentages of polymorphic loci of the plants from two tableland gardens were 13.77% (Yunkang 10) and 24.2% (Menghai Daye), respectively. There was a great genetic difference between ancient tea gardens and tableland tea gardens. The genetic diversity among the plants of the ancient tea garden was higher than those of the sexual tableland tea garden and the clone tableland tea garden based on P valve. The four ancient tea gardens and two tableland gardens could be differentiated with AFLP markers. The results show that AFLP marker is an effective tool in the discrimination of tea germplasm, as well as sundried green tea.