[The analysis of unconventional lymph node metastasis in tongue squamous cell carcinoma].

Objective: To analyze the characteristics of cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: A retrospective study was conducted. A total of 329 patients with TSCC who underwent en bloc resection of primary tumor and neck dissection in the Second Xiangya Hospital of Central South University from June 2010 to March 2018 were included. There were 283 males and 46 females, aged from 26 to 80 years. All patients underwent the modified neck dissection. The main difference between the modified neck dissection and the traditional neck dissection lay in the managements of unconventional lymph nodes. The lymphatic adipose tissues adjacent to the superior thyroid artery, the base of facial artery and the branches of external carotid artery were thoroughly dissected. The primary tumor as well as lingual artery, tissues along the lingual artery and lymph nodes in the mouth floor were resected. χ2 test was used for comparison of count data, and linear regression model was used for multivariate analysis. Results: Cervical lymph node metastases were found in 136 patients (41.3%). Among 142 patients (T1-2cN0) with supraomohyoid neck dissection, 22 patients had pathologically occult lymph node metastases (15.5%), with a 5-year overall survival rate of 90.2%, which was similar to the 5-year overall survival rate of 92.1% in 120 patients without lymph node metastasis (χ2=0.156, P=0.693). Multivariate linear regression analysis showed that T stage, clinical stage and unconventional lymph node metastasis were important factors for cervical lymph node metastasis in tongue cancer patients (P<0.05). Unconventional lymph node metastases occurred in 30 patients (9.1%), including the metastases of lymph nodes in the floor of mouth (3.0%), the lingual artery (2.4%), the base of the external maxillary artery (2.1%), the superior thyroid artery (0.9%), and the external carotid artery (0.6%). There were significant differences in the unconventional lymph node metastasis rates between patients with negative and positive conventional lymph node metastases [4.9%(10/203) vs. 15.9%(20/126), χ2=11.242, P=0.001] and also between patients with depth of invasion ≤5 mm, 5 mm 10 mm [3.1%(2/64) vs. 5.7%(6/106) vs. 13.8%(22/159), χ2=7.907, P=0.005]. Conclusion: Supraomohyoid neck dissection can achieve reliable control efficacy in patients with cN0 tongue cancer. All patients with lymph node dissection should undergo unconventional lymph node dissection. Unconventional lymph node dissection is strongly recommended for patients with conventional lymph node metastasis.

[Free anterolateral thigh flap with superficial temporal vessels as recipient vessels for reconstruction of defect after maxillectomy in malignant tumor].

Objective: To study the effects of superficial temporal artery and vein as recipient vessels for the free anterolateral thigh flap on the appearance and functions after maxillectomy. Methods: Clinical data of 21 patients with malignant maxillary tumors in Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University from January 2014 to November 2019, who were treated by free anterolateral thigh flap with temporal superficial vessels as the recipient vessels were analyzed retrospectively. There were 18 males and 3 females, with the age ranging from 29 to 73 years old, including 19 cases of squamous carcinoma, 1 case of adenoid cystic carcinoma and 1 case of osteosarcoma. Of those 7 patients underwent primary surgery, 14 patients received resurgery, and 6 patients had a history of postoperative radiotherapy and chemotherapy. Among 14 patients with resurgery, 13 had recurrent ipsilateral second site tumor and 1 had recurrent tumor, and all of them received the maxillectomy and reconstructive surgery with the free anterolateral thigh flap. Patients were evaluated with water swallow test and speech intelligibility score in 1, 3 and 6 months after operation. The data were statistically analyzed with SPSS 22.0 statistical software. Water swallow test results before and after operation were compared using the Wilcoxon rank sum test. The mean speech intelligibility scores before and after operation were compared by the paired t test. Results: Patients were followed up for 10-60 months. All free flaps survived after operation. No diplopia occurred. Breathing, swallowing and speaking functions were normal. No movement disorders caused by the donor of thigh flap. Water swallow test showed no phenomenon of water flowing into the nasal cavity or oral and nasal leakage with level Ⅰ for 4 cases, level Ⅱ for 13 cases, level Ⅲ for 3 cases and level Ⅳ for 1 case. The mean speech intelligibility scores before surgery and 1, 3 and 6 months after surgery were 4.31±0.13, 1.46±0.21, 2.15±0.45 and 2.87±0.76 respectively. There was statistically significant difference in the mean speech intelligibility scores between 1 and 6 months after surgery (F=78.456, P<0.05). Conclusion: It is safe and reliable to use the superficial temporal vessels as recipient vessels for free anterolateral thigh flap in the reconstruction of defect after maxillectomy in malignant tumors, with good outcomes of functions and a satisfactory restoration of outward appearance.

[Clinicopathological features and prognosis of nodal nevi].

Objective: To investigate the clinicopathological characteristics, differential diagnosis and prognosis of nodal nevi (NN). Methods: Eighteen cases of NN diagnosed at Fudan University Shanghai Cancer Center, Shanghai, China from 2009 to 2019 were collected. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. The Vysis Melanoma FISH Probe Kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed in 2 cases. Results: There were 2 males and 16 females in the case series. The age of the patients ranged from 36 to 70 years (average 48.2 years). Fifteen cases located in axillary lymph nodes, 1 in inguinal lymph node, 1 in cervical lymph node, and 1 in external iliac lymph node. NN was found in only one lymph node in each case. Histologically, the nevus cell aggregates were found in capsule of lymph nodes in all cases. Nevus cells grew along the capsule into trabeculae in 8 cases, with 3 of them scattered in parenchyma. In one of these 8 cases, nevus cell aggregates massively occupied the parenchyma of the lymph node. The largest lesions in the 18 NN cases measured from 0.2 to 6.5 mm. All of the NN cases were classified as conventional nevi. The majority of the cases were composed of uniform nevus-like cells and identical to cutaneous pigmented nevi without atypia, necrosis, or mitosis. In the NN case that massively occupied parenchyma, some areas had abundant nevus cells and displayed atypical cytologic features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry was performed in 13 cases. All of them were positive for S-100, SOX10, Melan A, and p16. HMB45 showed weak staining in rare cells of only one case out of 13 cases. Ki-67 labeling index <1% was found in all 13 cases. Additionally, the results of FISH assay were both negative. All patients were followed up for 13 to 129 months (median 31.5 months). Except that one patient died of the salivary gland carcinoma, the other patients all survived without tumor during the follow-up period. Conclusions: NN is a benign melanocytic lesion in lymph node. It is important to distinguish NN from metastatic melanoma when nevus cells occur in parenchyma and subcapsular sinus of lymph nodes, or show some atypical cytologic features. The morphology of bland nevus cells in capsule and trabeculae is a valuable clue. Besides, immunohistochemical profiling and FISH assay are helpful in the differential diagnosis.

[Efficacy analysis of fully endoscopic microvascular decompression in primary trigeminal neuralgia via keyhole approach].

Objective: To explore the efficacy and technical features of fully endoscopic microvascular decompression(MVD) in primary trigeminal neuralgia(PTN) via keyhole approach. Methods: The clinical data of 97 patients with PTN underwent fully endoscopic MVD via keyhole approach in the Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University from December 2014 to February 2019 was collected. During fully endoscopic MVD in PTN via keyhole approach, performer use natural clearance without grinding except developed rock bone crest or excessive retraction of the brain tissue, visually and panoramically observe and evaluate the CPA area, accurately identify the responsible vessels, to avoid the omission of responsible vessels or insufficient decompression. And the use of preplaced technology, bridging technology and submersible technology, ensure the efficacy of surgery and reduce the surgical side injuries.Barrow Neurological Institute (BNI) pain score was used to evaluate the efficacy and identify the recurrence. The surgical efficacy was analyzed. Results: The offending vessels were identified under endoscope in 96 cases. Among them, arterial compression was found in 77 cases, venous compression in 6 cases, and both arterial and venous compression in 13 cases. About the pain outcomes, 87 cases had immediate and complete relief of pain, 5 cases had almost relief of pain, 4 cases had partial relief of pain, and still needed medication control, but the dose was lower than that before operation, and 1 case had no obvious relief of pain. About complications, there were 4 cases of temporary facial numbness, 1 case of temporary hearing loss, both of them recovered after symptomatic treatment. There was no cerebral infarction or hemorrhage, intracranial or incision infection. All cases were followed up for 3.0-38.0 months with a median period of(22.4±2.2) months. During the follow-up periods, postoperative recurrence occurred in 3 cases. Conclusion: Fully endoscopic MVD for PTN through keyhole approach, provides panoramic view to avoid omission of offending vessels and reduce complications, seemed to be a safe and effective surgical method.

SOCS2 affects the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating EphA1.

Although the incidence of nasopharyngeal carcinoma (NPC) is relatively low, the mortality is very high and the patients have a poor prognosis. Thus, it is urgent to find a novel biomarker and a new therapeutic strategy. Suppressor of cytokine signaling-2 (SOCS2) was reported to be associated with various malignancies. However, the exact role of SOCS2 in NPC still remains largely unsure. In the present study, we showed that the expression of SOCS2 was significantly upregulated in NPC patients and cells. And the high expression of SOCS2 predicted a worse outcome in NPC patients. Moreover, the in vivo experiments indicated that knockout of SOCS2 inhibits the proliferation, migration, and invasion of NPC cells. Besides, we found a positive relationship between SOCS2 and EphA1 in NPC tissues. The rescue experiments indicated that SOCS2 affected the malignancy of NPC cells by regulating the expression of EphA1. Altogether, our data uncovered the ontogenetic role of SOCS2 dysregulation during the tumorigenesis of NPC. SOCS2 might serve as a biomarker during the diagnosis and treatment of NPC. And targeting SOCS2 might provide a novel treatment strategy for NPC patients.

[The prostate cancer precision screening program: a preliminary report after recruitment of 2 159 men].

Objective: The Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group released Consensus of prostate cancer (PCa) screening in 2017. This program aims to evaluate the methods and significance of prostate cancer precision screening in high risk population. Methods: A total of 2 159 eligible males enrolled from 13 community centers and 3 screening centers received PSA test from April 2017 to August 2018. Prostate-specific antigen (PSA) determination in serum with a cut-off of ≥4.0 ng/ml was the main screening test and indication for biopsy. The interviewer-administered questionnaire covered demographic characteristics and environmental exposure factors. The associations between these factors and prostate cancer risk were determined by multivariable unconditional logistic regression models. Results: Altogether, 271 cases (12.6%) had a confirmed PSA increase ≥ 4.0 µg/L (median 9.1, range 4.0-25.0). Subsequently, 57 subjects (21.0%) out of the 271 PSA-suspicious men underwent prostate biopsy, and 34 (59.6%) were confirmed as prostate cancer. Until now, the overall prostate cancer incidence in the first screening round was1.57%. There were no statistical differences in the distributions of PSA-suspicious and prostate cancer incidence between community centers and screening centers (P=0.578 and 0.735). Age (OR: 2.63; 95%CI: 1.84-3.75, P<0.001) and chronic prostatitis history (OR: 2.02; 95%CI: 1.55-2.63, P<0.001) were significantly associated with PSA level. After adjustment for these factors, older age (OR: 4.04; 95%CI: 1.71-9.59, P=0.002) and statins use (OR: 3.09; 95%CI: 1.25-7.69, P=0.015) were associated with an elevated risk of PCa. Conclusions: It is of substantial significance to screen prostate cancer in high risk population. Both community centers and screening centers methods are effective. Although largely underestimated, the incidence of PCa in the targeted Chinese population is higher than expected. Older men have a high risk of harboring PCa. Our study suggests a decreased risk of PCa in men with statins use. Prostate Cancer Precision Screening is promising to improve prostate cancer survival in China.

[Application of complete endoscopic technique in microvascular decompression related tovertebrobasilar artery compression].

Objective: To study the operative method, special technique and curative effect of complete neuroendoscopic microvascular decompression(MVD) related to vertebrobasilar artery compression. Methods: Thirteen patients with functional cranial nerve disease caused by vertebrobasilar artery as direct or indirect responsible vessel accepted complete endoscopic MVD, including 11 patients with hemifacial spasm and 2 patients with trigeminal neuralgia. The procedure and curative effect of endoscopic surgery were analyzed retrospectively. Results: All procedures of complete neuroendoscopic MVD were successfully completed.Intraoperative observation by endoscope showed that 6 cases were oppressed directly by vertebral artery, 2 cases were oppressed directly by basilar artery, 5 cases were combined oppressed by displaced basilar artery and other vessels (1 case was superior cerebellar artery and 4 cases were anterior inferior cerebellar artery). During the operation, Teflon sheets was placed directly into the compression point in 2 cases, the "Pre-placed" technique was used to place Teflon sheets in 7 cases, and the "Set up bridge" technique was used to place Teflon sheets in 4 cases. Follow-up for 8-38 months,the symptoms disappeared completely in 12 cases and improved in 1 case. No deaths and severe complications occurred, such as postoperative bleeding, cerebellar infarction and intracranial infection. Conclusion: MVD related to vertebrobasilar artery compression can be performed by complete neuroendoscopic technique, which can achieve sufficient decompression effect and curative effect.Flexible use of the special technology of placing Teflon sheets by single-hand under endoscope, such as the "Pre-placed" and "Set up bridge" technique, is an important technical guarantee for the successful completion of endoscopic MVD.

[Chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer: a short-term efficacy and safety analysis].

Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q(R))) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m(2) intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) µg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 µg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 µg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions: The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

[Efficacy analysis of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma].

Objective: To investigate the efficacy of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma (CSDH). Methods: A retrospective analysis of 201 cases of CSDH diagnosed and treated at Beijing Shijitan Hospital (CMU) from January 2006 to December 2017 was conducted. From January 2006 to December 2010, 126 cases of CSDH were treated with skull drilling and drainage (non-endoscopic group). From January 2011 to December 2017, 75 cases of CSDH were treated with soft neuroendoscopy (endoscopic group). The operation time of the non-endoscopic and endoscopic groups, the hematoma clearance rate on the first day after surgery, the time of the drainage tube, the length of hospital stay, the incidence of complications, mortality and recurrence rate were compared. Results: There were no deaths in both groups. The average operation time of the non-endoscopic group was 43 min, compared with the average operation time of the endoscopy group of 50 min, there was no significant difference (P>0.05). The average hematoma clearance rate on the first day after surgery in the endoscopy group (98.2%) was significantly higher than that in non-endoscopic group (87.3%) (P<0.01). The average time of drainage tube in the endoscopy group (23 h) was significantly shorter than that in the non-endoscopic group (50 h) (P<0.01). On the first postoperative day, the proportion of patients with mRS≤3 in the endoscopic group was significantly higher than that in the non-endoscopic group (P<0.01). At the time of discharge, the proportion of patients with mRS≤3 in the endoscopy group was also significantly higher than that in the non-endoscopic group, P<0.05. There was no significant difference in the average hospital stay between endoscopy group (7 d) and non-endoscopic group (8 d) (P>0.05). The postoperative complication rate in the endoscopy group was significantly lower than that in the non-endoscopic group (P<0.01). During 0.5-8 years of follow-up, the recurrence rate of CSDH in the endoscopic group (5.33%) was significantly lower than that in the non-endoscopic group (15.07%) (P<0.01). Conclusion: The application of visualization features of soft neuroendoscopy in the treatment of CSDH can significantly improve hematoma clearance, shorten the time of drainage tube, reduce postoperative complications and recurrence rate, and improve surgical outcomes.

microRNA-1205 promotes cell growth by targeting APC2 in lung adenocarcinoma.

OBJECTIVE: An increasing amount of evidence indicates that microRNAs (miRNAs) can be potential diagnostic and prognostic markers for various cancers. In this study, a novel miRNA, miR-1205, was identified in lung adenocarcinoma (LUAD). PATIENTS AND METHODS: First, the expression of miR-1205 in tissues was determined and verified to be correlated with the prognosis of patients. Overexpression and knockdown in LUAD cells were chosen to evaluate the effect of miR-1205 on cell growth in vitro. Luciferase assays, Western blot and rescue assays were performed to screen and confirm potential targets of miR-1205. RESULTS: We demonstrated that miR-1205 was down-regulated in the tissues of LUAD, and that miR-1205 may be a predictor of overall survival of LUAD. The overexpression of miR-1205 promoted cell proliferation and colony formation. Our results indicated that miR-1205 targeted APC2 directly, serving as a vital part in accelerating LUAD cell proliferation. CONCLUSIONS: We showed that miR-1205 could promote LUAD cell growth by targeting APC2 protein expression and provided further proof of miR-1205 as a potential non-invasive biomarker and therapeutic target for LUAD.

[Two cases of piriform pit carcinoma were repaired with thyroid lobe].

Two cases with piriform fossa cancer underwent larynx lateral wall repair surgery. Case 1: The patient was admitted to the hospital because of pharyngeal discomfort with swallowing pain for 2 months Electronic laryngoscopy revealed neoplasm in the left piriform fossa. Space occupying lesion in left piriform fossa and paranasal space was found in MRI scan. The pathological diagnosis of this patient was squamous cell squamous cell carcinoma (T2N1M0). Case 2: The patient was admitted to the hospital because of blood in the sputum for more than 1 year. The electronic laryngoscope suggested neoplasm in the pharyngeal space and left vocal cord paralysis.Soft tissue thickening of the oropharynx and hypopharyngeal right wall was found in MRI scan. The pathological diagnosis of this patient was squamous cell carcinoma (T1N2M0).

MiR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in glioma.

OBJECTIVE: miRNAs have been confirmed to be related to cell proliferation and apoptosis. In this study, we detected the potential effect of miR-448 on glioma cell proliferation and apoptosis. MATERIALS AND METHODS: miR-448 and CTTN expression levels were detected in glioma cell lines with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cells were transfected with miR-448 mimics and inhibitor by using lipofectamine 2000 respectively. The proliferative ability of transfected cells was detected via methyl thiazolyl tetrazolium (MTT) and cell counting kit-8 (CCK8) assays. Cell apoptosis and cell-cycle were tested using flow cytometry. The regulatory correlation between miR-448 and CTTN was explored by bioinformatics analysis and luciferase reporter assay. RESULTS: Lower expression of miR-448 and higher level of CTTN were detected in glioma cells. MiR-448 could regulate cell proliferation, cell apoptosis, and cell cycle. CTTN was negatively regulated by miR-448. CONCLUSIONS: miR-448 downregulates CTTN to inhibit cell proliferation and promote apoptosis in glioma, which indicates a potential therapeutic target of glioma.

Identification of the novel HLA-DQB1*03:181 allele in a Chinese leukemia patient.

HLA-DQB1*03:181 has one nucleotide change from HLA-DQB1*03:05:01 at position 470C>G.

[Use of prostate health index in diagnosing prostate cancer in Chinese men].

Objective: To investigate the value of prostate health index (PHI) in the diagnosis of prostate cancer in patients with total prostate specific antigen (tPSA) <20 µg/L. Methods: Totally 1 135 patients with tPSA<20 µg/L and prostate biopsy indications at Department of Urology, Fudan University Shanghai Cancer Center from March 2013 to April 2016 were enrolled in this study. They were tested for serum tPSA, free prostate specific antigen and prostate specific antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and tPSA were evaluated using receiver operating characteristic (ROC) curve analysis. The detection rates of prostate cancer were calculated in different ranges of PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in the range of 4 to 10 µg/L and digital rectal examination negative, was performed. Results: In the biopsied objects with tPSA<20 µg/L, PHI was significantly higher in prostate cancer patients than that in non-cancer patients (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly higher in high-grade prostate cancer patients than that of low-grade prostate cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 9.4% (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to 37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed that the AUC of PHI in diagnosing prostate cancer was significantly higher than that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 8.1% (95%CI: 5.4% to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8% (95%CI: 66.7% to 88.9%), respectively. Conclusion: PHI is superior to tPSA in the diagnosis of prostate cancer in Chinese men with tPSA<20 µg/L.

Rheumatoid arthritis fibroblast-like synoviocytes co-cultured with PBMC increased peripheral CD4+ CXCR5+ ICOS+ T cell numbers.

'Circulating' T follicular helper cells (Tfh), characterized by their surface phenotypes CD4+ chemokine receptor 5 (CXCR5)+ inducible co-stimulatory molecule (ICOS)+ , have been identified as the CD4+ T cell subset specialized in supporting the activation, expansion and differentiation of B cells. Fibroblast-like synoviocytes (FLS) are critical in promoting inflammation and cartilage destruction in rheumatoid arthritis (RA), and the interaction between FLS and T cells is considered to facilitate FLS activation and T cell recruitment. However, it remains unknown whether RA-FLS co-cultured with activated peripheral blood mononuclear cells (PBMC) has immunoregulatory effects on peripheral Tfh. In the present study, we co-cultured RA-FLS with or without anti-CD3/CD28-stimulated PBMC. The results showed that RA-FLS co-cultured with stimulated PBMC could increase the numbers of CD4+ CXCR5+ ICOS+ T cells of RA PBMC possibly via the production of interleukin (IL)-6, a critical cytokine involved in the differentiation of Tfh cells. We also observed increased reactive oxygen species (ROS) levels in the co-culture system of RA-FLS and PBMC. The percentage of CD4+ CXCR5+ ICOS+ T cells was decreased when ROS production was inhibited by N-acetyl-L-cysteine (NAC), a specific inhibitor which can decrease ROS production. In addition, we showed that the higher levels of tumour necrosis factor (TNF)-α and IL-1ß in the co-culture system and the blocking of TNF receptor 2 (TNF-R2) and IL-1ß receptor (IL-1ßR) both decreased the numbers of CD4+ CXCR5+ ICOS+ T cells. Our study reveals a novel mechanistic insight into how the interaction of RA-FLS and PBMC participates in the RA pathogenesis, and also provides support for the biologicals application for RA.

Prolonged exposure to extracellular lumican restrains pancreatic adenocarcinoma growth.

We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance. Importantly, extracellular lumican is associated with diminished ERK1/2 phosphorylation and increased p38 phosphorylation within PDAC cells. We further demonstrated that extracellular lumican physically binds with EGFR to trigger EGFR internalization and downregulation of EGFR and its downstream signal molecule ERK. Lumican enhances casitas B-lineage lymphoma expression, which stabilized the TGFß Type II receptor sensitizing PDAC cells to TGFß-mediated activation of p38 and SMAD signals. These provide a mechanism for the shift in signalling and phenotypic changes we observed after prolonged exposure to lumican. Together, our findings demonstrate that stromal lumican restrains PDAC cell growth through mediating cell entry into a quiescent state.

Comparative study: efficacy of closed-looptarget controlled infusion of cisatracurium and other administration methods for spinal surgery of elderly patients.

OBJECTIVE: To observe the efficacy of traditional administration, continuous pump injection, and closed-loop target controlled infusion of cisatracurium to determine the optimal method of drug administration, and to establish the individualized and rational administration of muscle relaxants in elderly patients. PATIENTS AND METHODS: A total of 150 patients who underwent spinal surgery under tracheal intubation general anesthesia in our hospital from August 2013 to April 2015 were selected. All patients were administered with general anesthesia and randomly divided into three groups: group A (n = 50) was treated under closed-loop target controlled infusion (CLTCI), group B (n = 50) was treated under muscle relaxation monitoring, and group C (n = 50) was treated under continuous pump injection. Hemodynamic changes and blood oxygen saturation of the three groups were observed, and the muscle relaxation recovery, dosage, and bleeding of the three groups were compared. RESULTS: MAP and HR of group A were significantly lower than those of group B and group C (p < 0.05). There were no cases of insufficient muscle relaxation in group A, five cases in group C, and 14 cases in group B, and the differences between any two groups were statistically significant (p < 0.05). Regarding muscle relaxation recovery, the time (T¬¬1) of recovery from 10%-25% and 25%-75%, and the time from drug withdrawal to recovery to TOFr from 0.7-0.9 of group A were the shortest, followed by group C and group B. The differences between any two groups were statistically significant (p < 0.05). The total dosage of cisatracurium of group A was the least, followed by group C and group B, and differences between any two groups were statistically significant (p < 0.05). Moreover, the bleeding volume of group A (235.2 ± 141.3 ml) was smaller than in group B (353.1 ± 173.8 ml) and group C (316.5 ± 155.2 ml), and differences between the three groups were statistically significant (p < 0.05). CONCLUSIONS: For spinal surgery of elderly patients, closed-loop target controlled infusion of cisatracurium was superior to continuous infusion and intravenous injection. The time of muscle relaxation recovery was shortened, the dosage of cisatracurium was reduced, and the number of cases of insufficient muscle relaxation was reduced.

[Analysis of the recurrence related factors of sinonasal inverted papilloma].

Objective:To evaluate the influence risk factors of recurrence and the methods for reducing recurrence of sinonasal inverted papilloma (SNIP). Method:Clinical data of 34 patients with SNIP were analyzed retrospectively. All of them were unilateral onset. The diagnosis was confirmed pathologically and the range of lesions was determined by endoscopic and imaging examination; clinical classification according to Krouse classification method; All operations were performed under nasal endoscope, of which 20 cases were operated by simple nasal endoscope, and 14 cases were operated by endoscopic anterior lacrimal recess approach. The patients were followed up for 12-36 months. The curative effects were observed and the prognostic factors of the patients were analyzed. Result:Thirty-four cases of SNIP patients with postoperative recurrence rate was 17.65% (6/34); simple nasal endoscopic surgery in 20 cases, the recurrence rate was 25.00%(5/20); endoscopic anterior lacrimal recess approach in 14 cases, the recurrence rate was 7.14%(1/14), the difference was statistically insignificant (χ²=1.807, P>0.05). Four cases in stage Ⅰ had no recurrence；20 cases in stage Ⅱ, the recurrence rate was 15.0%(3/20); 9 cases in stage Ⅲ, the recurrence rate was 33.3%(3/9); 1 case in stage Ⅳ had no recurrence, the recurrence rate of the patients with different stages were statistically insignificant (χ²=2.692, P>0.05). Conclusion:Simple endoscopic resection of the tumor and endoscopic anterior lacrimal recess surgery are effective methods for the treatment of SNIP. The nasal surgery history and tumor origin are the risk factors for recurrence. The operation completely tumorresection,detailed preoperative examination and postoperative regular endoscopic examination are the keys to preventing recurrence.

Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients.

Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre-operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure.

Extracellular lumican augments cytotoxicity of chemotherapy in pancreatic ductal adenocarcinoma cells via autophagy inhibition.

Lumican, an extracellular matrix proteoglycan overexpressed by pancreatic stellate cells (PSCs) and pancreatic ductal adenocarcinoma cells (PDACs), drives the formation of a tumor-specific microenvironment. We recently showed that extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery. Here we investigated the role of extracellular lumican in chemotherapy-mediated cancer therapy. Lumican secretion was increased by chemotherapeutic agents in PDAC, and especially in PSCs, and appeared to be linked to the extent of cells' response to chemotherapy-induced growth inhibition. In multiple PDAC models, including cell lines, patient-derived xenografts and lumican knockout mice, lumican significantly increased antitumor effect of chemotherapy. This effect was associated with DNA damage, apoptosis and inhibition of cell viability, glucose consumption, lactate production and vascular endothelial growth factor secretion. In PDAC cells, chemotherapeutic agents triggered autophagosome formation and increased LC3 expression through the reactive oxygen species-mediated AMP-activated kinase (AMPK) signaling pathway. Inhibition of gemcitabine-induced autophagy in cancer cells by treatment with AMPK inhibitor compound C, lysosomal inhibitor chloroquine or autophagy inhibitor 3MA enhanced gemcitabine-induced apoptosis, suggesting that autophagy is a protective cellular response to gemcitabine treatment. Importantly, lumican dramatically decreased AMPK activity, inhibiting chemotherapy-induced autophagy in both in vitro and in vivo PDAC models. Co-treatment of PDAC cells with lumican and gemcitabine increased mitochondrial damage, reactive oxygen species (ROS) production and cytochrome c release, indicating that lumican-induced disruption of mitochondrial function may be the mechanism of sensitization to gemcitabine. Together, our findings demonstrate that extracellular lumican augments cytotoxicity of chemotherapy in PDAC cells through inhibition of chemotherapeutic agent-induced autophagy.