[Research progress on the role of glucose in regulating immune homeostasis].

Glucose is the central nutrient for energy metabolism and life support in the human body. As the main energy substance of the body, glucose is essential for the normal function of immune cells and their proliferation; when glucose homeostasis is disrupted in the body, it may lead to impaired immune system function and pathological conditions. Exploring the relationship between glucose metabolism and immune regulation can help establish the gene regulatory network and figure out potential pathogenic mechanisms under physiological and pathological conditions. This article reviews the current scientific research progress on glucose metabolism and immunity, mainly focusing on the physiological regulatory functions of glucose in maintaining the homeostasis of innate and acquired immunity; and summarizes the research progress on the effects and mechanisms of glucose on tumor immunity and its related therapies under pathological conditions, taking tumors as an example.

[Anti-HMGCR immune-mediated necrotizing myopathy: A case report].

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

[Research progress on proactive healthy lifestyle and disease immunoprevention].

The paradox of increasing health needs and limited health resources prompted a change in the traditional concept of disease prevention and control, and the concept of proactive health has emerged. Proactive health aimed to prevent and control disease and improve the body's immunity by using controlled methods and means to activate the body's self-healing ability and to identify foreign harmful substances as well as damage factors and tumor cells that the body itself may produce while giving full play to individual initiative. With the continuous development of science, people could maintain and improve their immune system from many aspects, which could be roughly divided into nonpharmaceutical interventions and pharmaceutical interventions. Nonpharmacological interventions included changing lifestyles and habits, adjusting the nutritional structure and intake of food, regulating mindsets and emotions, and improving the living and working environment, etc. This review systematically elaborated on the functions and molecular mechanisms of nutrition, exercise, sleep, and emotion in regulating immunity, to provide some scientific evidence and theoretical support for proactive health.

[hsa_circ_0000231 affects the progression of tongue squamous cell carcinoma by activating Wnt/ß-catenin signaling pathway].

Objective: To explore the action mechanism of hsa_circ_0000231 in the occurrence and development of tongue squamous cell carcinoma (TSCC). Methods: Tissue samples of 60 TSCC patients were examined. The patients, including 32 males and 28 females, aged from 36 to 84 years old, underwent surgery in the Affiliated Hospital of Nantong University and Affiliated Tumor Hospital of Nantong University from December 2014 to December 2017. Saliva samples were obtained from healthy volunteers (5 males and 5 females, aged from 40 to 75 years old) and 10 TSCC patients. The TSCC cell lines (CAL-27, Tca-8113 and HN-4) were used. The expression levels of hsa_circ_0000231 in 60 pairs of freshly matched TSCC and para-carcinoma tissue samples, 10 pairs of saliva samples and 3 TSCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). hsa_circ_0000231 gene interference and lentiviral transfection were constructed, hsa_circ_0000231 in TSCC cell lines CAL-27 and Tca-8113 was knocked down, and the expressions of hsa_circ_0000231 in hsa_circ_0000231 interference group (sh-circ) and no-load lentivirus group (negative control) were tested with qRT-PCR. Cells with the highest knock-down efficiency were selected for CCK-8 test, colony formation assay, transwell invasion assay and scratch assay. The expressions of EMT-related proteins including E-cadherin, snail protein, N-cadherin and vimentin and proteins related to Wnt/ß-catenin signaling pathway including ß-catenin, C-myc, Bcl-2, MMP-9 and Cyclin D1 were measured by western blot. After TSCC cells in the interference group were co-cultured with Wnt/ß-catenin pathway activator LiCl, the expressions of above proteins were re-measured by western blot. TSCC cells in interference group and control group were subcutaneously injected into nude mice to compare the effect of hsa_circ_0000231 knockdown on the growths of the tumors grafted subcutaneously in the nude mice. Statistical analysis software 25.0 was used for data analysis, and t-test or chi-square test was used for comparison between groups. Results: hsa_circ_0000231 was highly expressed in the tissue and saliva samples of TSCC patients and cell lines CAL-27, Tca-8113 and HN-4, but lowly expressed in paired para-carcinoma tissues, saliva samples of healthy people and normal human oral keratinocytes (all P<0.05). Log-rank univariate analysis showed that hsa_circ_0000231 expression level, tumor differentiation degree and T stage were related to the survival of TSCC patients (all P<0.05). Multivariate Cox risk regression model analysis suggested that hsa_circ_0000231 expression level (χ2=5.77,P=0.016) and T stage (χ2=5.27,P=0.029) were independent factors for the poor prognosis of TSCC patients. Western blot showed the expressions of snail protein, N-cadherin and vimentin were down-regulated, but E-cadherin was up-regulated in interference group compared with control group. In interference group, the expressions of ß-catenin, C-myc, Bcl-2, MMP-9 and CyclinD1 were down-regulated, which were reversed after TSCC cells were co-cultured with LiCl. The knockdown of hsa_circ_0000231 reduced the proliferation, invasion and metastasis abilities of CAL-27 and Tca-8113 cells, which were reversed after TSCC cells were co-cultured with LiCl. The growth rate and volume of the tumors grafted subcutaneously in interference group using LiCl were greater than those in negative control group. Conclusion: hsa_circ_0000231 is an independent prognostic factor of TSCC. Highly expressed hsa_circ_0000231 can promote the proliferation, invasion and metastasis of TSCC cells.

Effect analysis of sacral canal therapy combined with Fufang Wulingzhi Tangjiang in the treatment of residual root pain after lumbar surgery.

OBJECTIVE: To observe the clinical effect of a combination of traditional Chinese and western medicine (sacral canal therapy combined with compound Fufang Wulingzhi Tangjiang) in the treatment of residual root pain after lumbar surgery. PATIENTS AND METHODS: From January 2019 to December 2020, 538 patients with residual root pain due to lumbar degenerative diseases were treated in our hospital [open decompression discectomy (ODD), Percutaneous Endoscopic Lumbar Discectomy (PELD) or Transforminal Lumbar Interbody Fusion (TLIF)]. They were randomly divided into control group (basic treatment + celecoxib), observation group 1 (basic treatment + compound Fufang Wulingzhi Tangjiang), observation group 2 (basic treatment + sacral canal therapy) and observation group 3 (basic treatment + sacral canal therapy + Fufang Wulingzhi Tangjiang). Follow-up 3-12 months. The therapeutic effect, VAS score, JOA score, treatment cost, complications, serum interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-α) were recorded and compared before treatment, 1 week after treatment, 2 weeks after treatment, 1 month after treatment, and the last follow-up. RESULTS: The treatment effect, VAS score, JOA, and treatment cost in the observation group were better than those in the control group (p < 0.05). There were significant differences in the above-mentioned indexes between the observation group 3 and the control group, observation group 1, and observation group 2 (p < 0 01). Inflammatory factors (IL-6, IL1, TNF-α) in the observation group were lower than those in the control group (p < 0 05). Inflammatory factors in observation group 3 were significantly lower than those in the control group, observation group 1, and observation group 2 (p < 0 01). CONCLUSIONS: Sacral canal injection combined with Fufang Wulingzhi Tangjiang can be effective in the treatment of postoperative root pain of lumbar degenerative diseases, which can reduce inflammatory factors such as IL-6, IL-1ß and TNF-α. It has the advantages of quick effect, short treatment time, low cost, high safety, in line with the concept of ERAS, easily accepted by patients and their families, and worthy of further popularizing and applying in clinic.

[Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology].

Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Investigation of the Inhibitory Effect of Platycodin D in Human Transitional Cell Carcinoma Cell Line 5637.

Platycodin D is an active component isolated from Chinese herb Platycodonis radix with various pharmacological activities, such as antitussive, expectorant, anti-inflammatory, and analgesic effects. Interestingly, platycodin D also exerts anticancer effects against several types of cancer. However, few studies on the anti-tumour effects of platycodin against urinary bladder cancer have been reported. In this study, we explored the anti-tumour effect of platycodin D against human bladder cancer and its mechanisms in vitro and in vivo. We found that platycodin D had significant anti-proliferative effects on four types of cancer cells, especially the 5637 bladder cancer cell line, and exerted these effects by preventing cell cycle progression from G0/G1 to S phase, down-regulating Ki-67 and cyclin D1 protein expression and up-regulating P21 protein expression. Furthermore, platycodin D inhibited 5637 cell migration by decreasing twist-related protein 1 (Twist1) and matrix metallopeptidase 2 (MMP2) expression and exerted significant tumour-suppressive effects in tumour-bearing nude mice. Platycodin D also increased caspase-9, caspase-8, caspase-3, and p53 expression and decreased Bcl-2 expression in tumour tissues. Taken together, our results provide a theoretical basis for application of platycodin D in treating urinary bladder cancer.

[Analysis of PARP inhibitors induced anemia in advanced and relapsed epithelial ovarian cancer].

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

MicroRNA-191-5p promotes the development of osteosarcoma via targeting EGR1 and activating the PI3K/AKT signaling pathway.

The article "MicroRNA-191-5p promotes the development of osteosarcoma via targeting EGR1 and activating the PI3K/AKT signaling pathway, by B. Chen, Z.-Y. Zheng, J.-Z. Yang, X.-G. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3611-3620-DOI: 10.26355/eurrev_201905_17783-PMID: 31114985" has been withdrawn from the authors due to some disagreements over the drafting of the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17783.

[Influential factors related to osteoradionecrosis of the mandible in oral and maxillofacial cancer patients following radiotherapy].

Objective: To identify risk factors associated with mandibular osteoradionecrosis (ORN) in oral and maxillofacial cancer patients following radiotherapty and to provide scientific basis for the etiological research and clinical prevention of mandibular ORN. Methods: A retrospective study was conducted in patients with oral and maxillofacial-head and neck cancer during the period from January 2013 to December 2015. Influential factors related to mandibular ORN were screened by single factor analysis, Lasso and Logistic regression analysis. Results: A total of 757 patients were analyzed, and the total incidence of mandibular ORN was 12.0%(91/757). There were 443 males and 314 females, aged (51.8±13.7) years. Thirty-five related factors were screened to 28 by single factor analysis. It was determined by Lasso regression analysis that, radiation doses (OR=1.135, P=0.034, 95%CI: 1.089-1.232), T classification (OR=2.586, P=0.001, 95%CI: 1.482-4.512), mandibular surgery (OR=9.101, P<0.001, 95%CI: 2.796-29.630), periodontitis (OR=6.089, P<0.001, 95%CI: 2.708-13.693), diabetes (OR=4.467, P=0.002, 95%CI: 1.705-11.704), tooth extraction after radiotherapy (OR=3.228, P=0.001, 95%CI: 1.640-6.350), dental caries (OR=2.911, P=0.009, 95%CI: 1.300-6.516), periapical periodontitis (OR=2.726, P=0.016, 95%CI: 1.209-6.145), smoking (OR=4.438, P=0.002, 95%CI: 1.702-11.571) and unilateral/bilateral radiotherapy (OR=2.225, P=0.028, 95%CI: 1.090-4.545) were significantly associated with developing mandibular ORN. Conclusions: Ten main risk factors for mandibular ORN were identified through the single center, large sample, retrospective analysis, which has a certain value for clinical prevention of mandibular ORN. Prospective, randomized controlled trials and long-term follow-up are still needed.

[Clinicopathological and survival analysis of 34 cases of uterine clear cell carcinoma].

Objective: To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC). Methods: UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS (P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS (P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients (P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage (P=0.009). Conclusions: The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

Fibroblast growth factor 18 alleviates hyperoxia-induced lung injury in mice by adjusting oxidative stress and inflammation.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants, but the ways to prevent and treat BPD are still very limited. We tried to find an effective method for treating BPD by studying the effect of fibroblast growth factor 18 (FGF18) on hyperoxia-induced lung injury in mice. MATERIALS AND METHODS: We placed newborn mice in high-oxygen environment (60-70%) and collected mouse lung tissue for histological examination at 3, 7, 14 and 21 days after birth. The correlation between FGF18 and BPD was studied by analyzing the expression of FGF18 in mouse lung tissue. In addition, we used exogenous FGF18 to stimulate primary mouse type II alveolar epithelial cells (AECs II), and detected changes in oxidative stress, inflammation and NF-κB signaling pathway activity of AECs II to analyze the effects of FGF18 on AECs II. RESULTS: From the 7th day after the birth of the mouse, the lung tissue of the hyperoxia-induced mice suffered significant lung injury relative to the control group. The expression of FGF18 in lung tissue induced by hyperoxia was lower than that in the control group. Cell viability of AECs II stimulated by exogenous FGF18 increased, and FGF18 also reduced oxidative stress and inflammation levels of AECs II and inhibited the AECs II injury caused by hyperoxia. NF-κB signaling pathway activity in hyperoxia-induced lung increased, while exogenous FGF18 could reduce the expression and phosphorylation of NF-κB p65 in AECs II. CONCLUSIONS: Hyperoxia-induced lung injury was accompanied by a decrease in FGF18. FGF18 can reduce oxidative stress and inflammation levels of AECs II by inhibiting the NF-κB signaling pathway, thereby reducing hyperoxia-induced cell injury.

Peanut (Arachis hypogaea L.) S-adenosylmethionine decarboxylase confers transgenic tobacco with elevated tolerance to salt stress.

Polyamines play an important role in stress response. In the pathway of polyamines synthesis, S-adenosylmethionine decarboxylase (SAMDC) is one of the key enzymes. In this study, a full length cDNA of SAMDC (AhSAMDC) was isolated from peanut (Arachis hypogaea L.). Phylogenetic analysis revealed high sequence similarity between AhSAMDC and SAMDC from other plants. In peanut seedlings exposed to sodium chloride (NaCl), the transcript level of AhSAMDC in roots was the highest at 24 h that decreased sharply at 72 and 96 h after 150 mM NaCl treatment. However, the expression of AhSAMDC in peanut leaves was significantly inhibited, and the transcript levels in leaves were not different compared with control These results implied the tissue-specific and time-specific expression of AhSAMDC. The physiological effects and functional mechanism of AhSAMDC were further evaluated by overexpressing AhSAMDC in tobaccos. The transgenic tobacco lines exhibited higher germination rate and longer root length under salt stress. Reduced membrane damage, higher antioxidant enzyme activity, and higher proline content were also observed in the transgenic tobacco seedlings. What's more, AhSAMDC also led to higher contents of spermidine and spermine, which can help to scavenge reactive oxygen species. Together, this study suggests that AhSAMDC enhances plant resistance to salt stress by improving polyamine content and alleviating membrane damage.

[Diagnosis, treatment and prognosis of uterine serous carcinoma].

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.

[Analysis of treatment and prognosis of 59 cases of vulvar melanoma].

Objective: To assess the treatment and prognosis of vulvar melanoma. Methods: A total of 59 cases of primary vulvar melanoma admitted to Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1st, 1981 to November 30th, 2019 were collected. The clinical characteristics, treatment, survival and prognostic factors of vulvar melanoma were analyzed retrospectively. The end date of follow-up was January 15th, 2020.The median follow-up time was 26.0 months (range:2-198 months). Results: (1) Clinical characteristics: the median age of 59 patients with vulvar melanoma was 56 years old (range:18-83 years old). According to the American Joint Committee on Cancer stage manual, there were 18, 7, 26 and 8 cases of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ respectively. The lesion of 38 cases was single and the other 21 cases were multiple. The largest diameter of the tumor ranged from 0.3 to 17.0 cm.The surface of the lesion was ulcerated in 17 cases. (2) Treatment: a total of 59 cases with vulvar melanoma, 56 patients received surgery, 36 cases of them received radical resection of vulva and 20 received local extended resection of vulvar tumor due to unilateral vulva lesion. Three patients did not receive surgery,one received chemotherapy combined with interferon, one received interferon, and one received radiotherapy. Lymph node management: among the 56 patients treated by surgery, 37 patients received inguinal lymphadenectomy, 24 (65%, 24/37) of whom were confirmed with inguinal lymph node metastasis by postoperative pathological examination. Inguinal lymph nodes enlargement were not found in 19 cases by preoperative imaging and clinical examination. In these 19 patients, three patients received inguinal lymph node biopsy, among them, one (1/3) patient was confirmed with inguinal lymph node metastasis by postoperative pathological examination, and the remaining 16 patients did not receive inguinal lymph node surgery. Postoperative adjuvant treatment: among the 56 patients who received surgery, 31 received adjuvant chemotherapy，one received adjuvant radiotherapy, four received interferon therapy, 17 received combination therapy including chemotherapy, and three did not receive postoperative adjuvant therapy. (3) Survival:during the follow-up period, the median survival time of 59 patients with vulvar melanoma was 30.0 months (range:2.0-198.0 months). The 3-year survival rate was 42.5%, and the 5-year survival rate was 23.8%. The median survival time of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 72.0, 45.0, 24.0 and 23.0 months, respectively. The difference among stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ were statistically significant （P<0.01）. The median survival time of patients undergoing radical resection of the vulva (35.0 months) and local enlarged tumor resection (29.0 months) were significantly longer than that of patients without surgery (9.0 months, P<0.01). The median survival time of the patients who underwent inguinal lymphadenectomy, lymph node biopsy and those who did not undergo surgery were 35.0, 32.0 and 30.0 months, respectively. There were no significant differences among the 3 groups (P>0.05). The median survival time of postoperative adjuvant chemotherapy patients (49.0 months) were significantly longer than that of postoperative adjuvant radiotherapy, interferon,and combination therapy including chemotherapy (9.0, 14.0 and 26.0 months, respectively, all P<0.01). (4) Prognostic factors: the univariate analysis showed that stage, vulvar operation and postoperative adjuvant treatment were the risk factors affecting the prognosis of patients with vulvar melanoma (P<0.01). Multivariate analysis revealed that stage alone was an independent risk factor affecting the prognosis of patients with vulvar melanoma (P<0.01). Conclusions: The prognosis of patients with vulvar melanoma is poor, and stage is an independent prognostic factor.Surgery combined with postoperative adjuvant chemotherapy may achieve relatively good results.

LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA, by Y. Kong, Y. Feng, Y.-Y. Xiao, S.-C. Liu, X.-G. Li, Q.-L. Yang, W.-H. Chu, J.-G. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4770-4776- DOI: 10.26355/eurrev_201906_18059-PMID: 31210306" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18059.

Potential effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on susceptibility to gastric cancer in Chinese population: a meta-analysis.

OBJECTIVE: This meta-analysis aims to clarify the effect of IL-17 polymorphisms on the susceptibility to GCa in the Chinese population. MATERIALS AND METHODS: Relevant pieces of literature were searched in PubMed, Web of School, VIP, and CNKI using the key words as "IL-17, gastric/stomach cancer" or "IL-17 polymorphisms, gastric/stomach cancer susceptibility". The odds ratio (OR) and 95% confidence interval (CI) in the selected studies were calculated using RevMan5.3 and STATA12.0. RESULTS: A total of 12 investigations reporting mutations in IL-17A rs2275913 and IL-17F rs763780 were enrolled. There were 11 studies reporting rs2275913 G>A, involving 3299 cases of GCa patients and 3339 cases of healthy controls. The random-effects model was performed since the heterogeneity test results of the recessive genetic model (GG&GA vs. AA) and the allelic model (G vs. A) of IL-17A rs2275913 G>A were I2>66%/p=0.001. Meanwhile, the dominant genetic model (GG vs. GA&AA) and the super-dominant genetic model (GA vs. GG&AA) of IL-17A rs2275913 G>A were I2< 50%/p>0.05, and the fixed-effects model was used. The meta-analysis showed that IL-17A rs2275913 G>A was positively correlated with GCa susceptibility under four genetic models (p<0.05). Five studies reporting IL-17F rs763780 T>C were enrolled, including 2535 cases of GCa patients and 2402 cases of healthy controls. The heterogeneity test showed that, except for the super-dominant genetic model, the p-value was <0.00001 in the dominant, recessive, and allelic models, and their I2 values were 87%, 88%, and 93%, respectively. Hence, a random-effects model was selected. IL-17F rs763780 T>C was positively correlated with GCa susceptibility under the super-dominant genetic model (p=0.003), rather than the other three models (p>0.05). CONCLUSIONS: IL-17A rs2275913 G>A polymorphism contributes to susceptibility to GCa in the dominant, recessive, allelic, and super-dominant models. Meanwhile, IL-17F rs763780 T>C polymorphism is positively correlated with GCa susceptibility in the super-dominant model.

[Analysis of effects and postoperative clinicopathological prognosis factors of neoadjuvant chemotherapy in patients with stage â b2 and â ¡a2 squamous cell carcinoma of the cervix].

Objective: To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods: A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2, Ⅱ a2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results: Of 177 patients, 133 (75.1%) had stage Ⅰb2 and 44 (24.9%) had Ⅱa2 cancers. After NACT, overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions: The effect of NACT in Ⅰ b2, Ⅱ a2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size >3 cm after NACT adversely affect 5-year OS rate.

[Efficacy and side effect analysis of paclitaxel liposome for neoadjuvant chemotherapy in locally advanced cervical cancer].

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.

LncRNA LUCAT1 promotes rowth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA.

OBJECTIVE: Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in the progression of tumorigenesis. This study aims to identify how lncRNA LUCAT1 functions in the progression of OSCC (oral squamous cell carcinoma). PATIENTS AND METHODS: Relative expression of lncRNA LUCAT1 in both OSCC cells and 50 paired tissue samples was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Moreover, biological function of LUCAT1 in OSCC was identified by performing transwell assay, wound healing assay and proliferation assay in vitro. The underlying mechanism was explored by qRT-PCR and Western blot. RESULTS: LUCAT1 expression was remarkably downregulated in OSCC tissues when compared with that in adjacent normal samples. Moreover, proliferation, invasion and migration of OSCC cells were inhibited after knockdown of LUCAT1 in vitro. Knockdown of LUCAT1 downregulated PCNA in OSCC cells at mRNA and protein level in vitro. Besides, PCNA expression in OSCC tissues was positively correlated with the expression of LUCAT1. CONCLUSIONS: Knockdown of LUCAT1 could inhibit migration, invasion and proliferation capacities of OSCC cells through downregulating PCNA, which may offer a new therapeutic intervention for OSCC patients.