[Marked improvement in rheumatoid lung nodules after treatment with tocilizumab combined with glucocorticoids and leflunomide: a case report and literature review].

Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by erosive inflammation of bone and cartilage, leading to progressive joint destruction. Pulmonary involvement occurs in approximately 60% of RA patients, manifests most commonly as interstitial lung disease and, less commonly, as rheumatoid lung nodules. Here, we report a 50-year-old woman, non-smoker, with recurrent cough and sputum of 7 years' duration, accompanied by a chest CT showing multiple cavitary nodules in both lungs. She had been treated empirically at several medical centers and was finally diagnosed with rheumatoid lung nodules. Marked improvement in rheumatoid lung nodules was observed after treatment with tocilizumab in combination with glucocorticoids and leflunomide. The aim of this study was to improve clinicians' understanding of rheumatoid lung nodules by analyzing the clinical features, diagnosis, and treatment of this case, and reviewing the relevant medical literature.

[Radiomics-based prediction of microsatellite instability in stage â ¡ and â ¢ rectal cancer patients based on T2WI MRI and diffusion-weighted imaging].

Objective: To examine the radiomics model based on high-resolution T2WI and diffusion weighted imaging (DWI) in predicting microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer. Methods: From February 2016 to October 2020, 175 patients with stage Ⅱ and Ⅲ rectal cancer who met the inclusion criteria were retrospectively collected. There were 119 males and 56 females, aged (63.9±9.4) years (range: 37 to 85 years), including 152 patients with microsatellite stability and 23 patients with microsatellite instability. All patients were randomly divided into the training group (n=123) and the validation group (n=52) with a ratio of 7∶3. The region of interest was labeled on the T2WI and DWI images of each patient using the ITK-SNAP software, and PyRadiomics was used to extract seven kinds of radiomics features. After removing redundant features and normalizing features, the least absolute shrinkage and selection operation were used for feature selection. One clinical model, three radiomics models and one clinical-radiomics model were constructed in the training group based on a support vector machine. The area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to evaluate the performance of the models in the verification group. Results: Three clinical features (age, degree of tumor differentiation, and distance from the lower edge of the tumor to the anal edge) and six radiomics features (two DWI-related features and four T2WI-related features) most related to microsatellite status of rectal cancer patients were selected. The AUC of the clinical-radiomics model in the training group was 0.95. In the validation group, the AUC was 0.81, better than the clinical model (0.68, Z=0.71, P=0.04), and equivalent to the T2WI+DWI model (0.82, Z=0.21, P=0.83). Conclusions: Radiomic features based on preoperative T2WI and DWI were related to microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer and showed a high classification efficiency. The model based on the features provided a noninvasive and convenient tool for preoperative determination of microsatellite stability in rectal cancer patients.

Characteristics of flight delays during solar flares.

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 106 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays.

Additional flight delays and magnetospheric-ionospheric disturbances during solar storms.

Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 106 records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications.

Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice.

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats.

The article "Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats, by L.-L. Guo, D.-S. Wang, Y.-Y. Xu, K.-G. Cui, published in Eur Rev Med Pharmacol Sci 2018; 22 (18): 6042-6048-DOI: 10.26355/eurrev_201809_15941-PMID: 30280789" has been withdrawn from the authors due to  substantial deficiency in the experimental design. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15941.

[Establishment and validation of a predictive nomogram model for advanced gastric cancer with perineural invasion].

Objective: Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan. Methods: Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P>0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results: A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 µg/L (OR=5.870, 95% CI: 3.281-10.502, P<0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P<0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P=0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P<0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P<0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P<0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 µg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results (P=0.415). Conclusion: A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Understanding the Functional Impact of VOC-Ozone Mixtures on the Chemistry of RNA in Epithelial Lung Cells.

Introduction: Ambient air pollution is associated with premature death caused by heart disease, stroke, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have suggested that ribonucleic acid (RNA) oxidation is a sensitive environment-related biomarker that is implicated in pathogenesis. Aims and Methods: We used a novel approach that integrated RNA-Seq analysis with detection by immunoprecipitation techniques of the prominent RNA oxidative modification 8-oxo-7,8-dihydroguanine (8-oxoG). Our goal was to uncover specific messenger RNA (mRNA) oxidation induced by mixtures of volatile organic compounds (VOCs) and ozone in healthy human epithelial lung cells. To this end, we exposed the BEAS-2B human epithelial lung cell line to the gas- and particle-phase products formed from reactions of 790 ppb acrolein (ACR) and 670 ppb methacrolein (MACR) with 4 ppm ozone. Results: Using this approach, we identified 222 potential direct targets of oxidation belonging to previously described pathways, as well as uncharacterized pathways, after air pollution exposures. We demonstrated the effect of our VOC-ozone mixtures on the morphology and actin cytoskeleton of lung cells, suggesting the influence of selective mRNA oxidation in members of pathways regulating physical components of the cells. In addition, we observed the influence of the VOC-ozone mixtures on metabolic cholesterol synthesis, likely implicated as a result of the incidence of mRNA oxidation and the deregulation of protein levels of squalene synthase (farnesyl-diphosphate farnesyltransferase 1 [FDFT1]), a key enzyme in endogenous cholesterol biosynthesis. Conclusions: Overall, our findings indicate that air pollution influences the accumulation of 8-oxoG in transcripts of epithelial lung cells that largely belong to stress-induced signaling and metabolic and structural pathways. A strength of the study was that it combined traditional transcriptome analysis with transcriptome-wide 8-oxoG mapping to facilitate the discovery of underlying processes not characterized by earlier approaches. Investigation of the processes mediated by air pollution oxidation of RNA molecules in primary cells and animal models needs to be explored in future studies. Our research has thus opened new avenues to further inform the relationship between atmospheric agents on the one hand and cellular responses on the other that are implicated in diseases.

[Application of convolutional neural network to risk evaluation of positive circumferential resection margin of rectal cancer by magnetic resonance imaging].

Objective: To explore the feasibility of using faster regional convolutional neural network (Faster R-CNN) to evaluate the status of circumferential resection margin (CRM) of rectal cancer in the magnetic resonance imaging (MRI). Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-1800017410). Case inclusion criteria: (1) the positive area of CRM was located between the plane of the levator ani, anal canal and peritoneal reflection; (2) rectal malignancy was confirmed by electronic colonoscopy and histopathological examination; (3) positive CRM was confirmed by postoperative pathology or preoperative high-resolution MRI. Exclusion criteria: patients after neoadjuvant therapy, recurrent cancer after surgery, poor quality images, giant tumor with extensive necrosis and tissue degeneration, and rectal tissue construction changes in previous pelvic surgery. According to the above criteria, MRI plain scan images of 350 patients with rectal cancer and positive CRM in The Affiliated Hospital of Qingdao University from July 2016 to June 2019 were collected. The patients were classified by gender and tumor position, and randomly assigned to the training group (300 cases) and the validation group (50 cases) at a ratio of 6:1 by computer random number method. The CRM positive region was identified on the T2WI image using the LabelImg software. The identified training group images were used to iteratively train and optimize parameters of the Faster R-CNN model until the network converged to obtain the best deep learning model. The test set data were used to evaluate the recognition performance of the artificial intelligence platform. The selected indicators included accuracy, sensitivity, positive predictive value, receiver operating characteristic (ROC) curves, areas under the ROC curves (AUC), and the time taken to identify a single image. Results: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CRM status determined by the trained Faster R-CNN artificial intelligence approach were 0.884, 0.857, 0.898, 0.807, and 0.926, respectively; the AUC was 0.934 (95% CI: 91.3% to 95.4%). The Faster R-CNN model's automatic recognition time for a single image was 0.2 s. Conclusion: The artificial intelligence model based on Faster R-CNN for the identification and segmentation of CRM-positive MRI images of rectal cancer is established, which can complete the risk assessment of CRM-positive areas caused by in-situ tumor invasion and has the application value of preliminary screening.

[The effect of perioperative ERAS pathway management on short-and long-term outcomes of gastric cancer patients].

Objective: To compare postoperative short-term outcomes and long-term prognosis between perioperative Enhanced Recovery After Surgery (ERAS) and conventional pathways protocols in gastric cancer patients. Methods: This is a single institute retrospective cohort study, all patients were pathologically proved to be gastric adenocarcinoma, underwent standard radical gastrectomy with D2 lymphadenectomy during the period of 2007-2012. Total 2124 cases were eligible to be analysed and divided into ERAS groups and Non-ERAS group according to the different perioperative pathway protocol. Propensity score matching method (in SPSS, 24.0 version, IBM Company) was used to balance the baseline characteristics. Two groups were matched in a 1∶1 ratio. There were 521 cases per group after matched. The short-term clinical outcomes (postoperative complications, length of hospital stay, blood loss, 30-day re-admission rate, etc.) and overall 5-year survival rates were compared between the two groups. Results: The incidence of overall postoperative complications was similar between the two groups (ERAS group=18.4%, non-ERAS group=19.4%, P=0.69), including anastomotic leakage, abdominal hemorrhage, etc. But the incidence of SSI, atelectasis, and thromboembolic disease in ERAS group was significant lower than that in Non-ERAS group. The number of lymph node harvested, operation time, intraoperative blood loss, postoperative hospital and cost in ERAS group were better than those in non-ERAS group. There were no significant differences in unplanned reoperation (ERAS group=3.1%, non-ERAS group=2.1%, P=0.33), 30 day readmission rate of discharge (ERAS group=6.1%, non-ERAS group=5.6%, P=0.69) and postoperative mortality (ERAS group=0.4%, non-ERAS group=0.2%, P=0.56) between the two groups. The 5-year overall survival rates of non-ERAS group and ERAS group were 66.2% and 72.8% respectively (P=0.007). The subgroup analysis found that 5-year OS rates of stage I were 93.4% and 92.7% (P=0.73), these of stage Ⅱ and Ⅲ were 82.2% vs 75.2% (P=0.007) and 47.6% vs 35.7% (P=0.02) in ERAS group and non-ERAS group respectively. Conclusions: Perioperative ERAS pathway management is safe and feasible for patients with gastric cancer, without increasing the incidence of complications and 30-day readmission rate. This protocol can improve the prognosis of patients with gastric cancer.

[Diagnostic value and patient compliance of a pancreas-oriented multidisciplinary clinic: a retrospective analysis from a Chinese pancreatic disease center].

Objective: To evaluate the role of multidisciplinary team (MDT) clinic in the diagnosis of pancreatic diseases and patient compliance with MDT advice in the current medical system. Methods: The study included 512 patients that had visited the pancreas-oriented MDT clinic of Zhongshan Hospital between May 2015 and May 2019.The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. Compliance was determined according to whether a patient received corresponding therapies or undergoing further checks or follow-ups. Results: Among the 512 patients that had visited the MDT clinic, 121 patients were referred due to undetermined diagnosis. Classified according to the final diagnosis, the rate of undetermined diagnosis in different disease categories from high to low in order was inflammatory diseases of the pancreas (75.0%, 24/32), other lesions of the pancreas (56.1%,23/41), pancreatic cystic lesions (19.1%,17/89), pancreatic carcinomas (18.3%,48/262) and pancreatic neuroendocrine neoplasms (pNEN)(10.2%,9/88). The MDT clinic made diagnosis to 68 patients directly with an accuracy of 89.7%. The rate of compliance in the entire cohort was 63.4%. The rate of compliance of patients from June 2017 to May 2019 (68.4%) was higher than that of patients from May 2015 to May 2017(59.6%). The compliance rate of patients in different disease categories from high to low in order was inflammatory diseases of the pancreas(84.4%, 27/32), pancreatic carcinomas (67.9%, 178/262), pNEN(60.2%,53/88), other lesions of the pancreas (56.1%,23/41), and pancreatic cystic lesions(49.4%, 44/89). The compliance rate of patients with different MDT advice from high to low in order was best supportive care(78.6%,22/28), antitumor approaches beyond surgery(71.6%,159/222), further tests(62.6%, 77/123), surgery(53.7%, 65/121) and follow-up(49.2%, 31/63). In patients suggested for surgery, the compliance rate of patients with carcinomas(67.4%, 33/49) was higher than patients with other kinds of neoplasms. Conclusions: MDT clinic could facilitate the diagnosis of pancreatic diseases conveniently and inexpensively. The overall compliance rate of MDT clinic patients is rather low, and patients with carcinomas have a relative high rate of compliance with the suggestion of surgery.

[Clinical application of convolutional neural network in pathological diagnosis of metastatic lymph nodes of gastric cancer].

Objective: To examine the value and clinical application of convolutional neural network in pathological diagnosis of metastatic lymph nodes of gastric cancer. Methods: Totally 124 patients with advanced gastric cancer who underwent radical gastrectomy plus D2 lymphadenectomy at Affiliated Hospital of Qingdao University from July 2016 to December 2018 were selected in the study. According to the chronological order, the first 80 cases were served as learning group. The remaining 44 cases were served as verification group. There were 45 males and 35 females in the study group, with average age of 57.6 years. There were 29 males and 15 females in the validation group, with average age of 9.2 years. The pre-training convolutional neural network architecture Resnet50 was trained and fine-tuned by 21 352 patches with cancer areas and 14 997 patches without cancer areas in the training group. A total of 78 whole-slide image served as a test dataset including positive (n=38) and negative (n=40) lymph nodes. The convolutional neural network computer-aided detection (CNN-CAD) system was used to analyze the ability of convolutional neural network system to screen metastatic lymph nodes at the level of slice by setting threshold, and evaluate the system's classification accuracy by calculating its sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Results: The classification accuracy of CNN-CAD system at slice level was 100%.The AUC for the CNN-CAD system was 0.89. The sensitivity was 0.778, specificity was 0.995, overall accuracy was 0.989. Positive and negative predictive values were 0.822 and 0.994, respectively. The CNN-CAD system achieved the same classification results as pathologists. Conclusions: The CNN-CAD system has been constructed to distinguished benign and malignant lymph node slides with high accuracy and specificity. It could achieve the similar classification results as pathologists.

[Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study].

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ(2) test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ(2)=288.60,P<0.01),N stage(χ(2)=68.10, P<0.01), vascular invasion(χ(2)=128.70, P<0.01)and neural invasion(χ(2)=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ(2)=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion: With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

[The value of preoperative CA19-9 combined with platelet-to-lymphocyte ratio in predicting invasive malignancy in intraductal papillary mucinous neoplasms].

Objective: To explore preoperative predictive markers for invasive malignancy in intraductal papillary mucinous neoplasm(IPMN). Methods: The retrospective case-controlled study was adopted.Seventy-nine patients who underwent surgery and with pathologically confirmed IPMN from January 2005 to December 2014 at Department of Pancreatic Surgery, Zhongshan Hospital Fudan University were enrolled.Forty-six patients were male and 33 were female,with an average age of (62.9±8.9)years (range:37-82 years).Tumor sites:56 tumors were located at the head of the pancreas,22 were located at the body and tail of the pancreas,and 1 was located across the whole pancreas.Surgical procedures: 51 patients underwent pancreaticoduodenectomy, 22 patients underwent distal pancreatectomy, 4 patients underwent segmental pancreatectomy and 2 patients underwent total pancreatectomy.IPMNs were classified into non-invasive lesions and invasive carcinomas according to the histopathological findings of the tumor.Thirty-two tumors were non-invasive lesions and 47 were invasive carcinomas.The preoperative findings were compared between patients with non-invasive IPMN and patients with invasive carcinoma by univariate analysis using t test and χ(2) test accordingly,and factors with statistically significance were subsequently submitted to multivariate analysis. Results: Univariate analysis showed that tumor size(P=0.022), carcinoembryonic antigen(P=0.012), CA19-9(P=0.011), lymphocytes(P=0.034), neutrophil-to-lymphocyte ratio(P=0.010)and platelet-to-lymphocyte ratio(PLR)(P=0.004)were predictive markers with statistical significance.Multivariate analysis showed that CA19-9(P=0.012)and PLR(P=0.025) were independent predictive markers for invasive malignancy in IPMN.The area under curve of the combination factor of CA19-9 and PLR(0.864) was larger than that of CA19-9(0.806) or PLR(0.685) alone, and all the authentic indicators of the combination factor were better than those of each alone. Conclusions: CA19-9 and PLR are independent predictive markers for invasive malignancy in IPMN.The combination of CA19-9 and PLR has improved efficacy than each alone.

[The expressions and diagnostic values of miR-18a and miR-21 in esophageal cancer].

Objective: To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma. Methods: The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum. Results: The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively. Conclusion: Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.

Effects of IL-1ß on hippocampus cell apoptosis and learning ability of vascular dementia rats.

OBJECTIVE: Vascular dementia (VD) is a type of memory, cognition, and behavior disorder caused by ischemic stroke or hemorrhagic stroke. It is a common pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation plays a key role in VD. Interleukin-1ß (IL-1ß) is a kind of pro-inflammatory cytokine, while its mechanism in VD occurrence and development is still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided into three groups, including sham group, VD model group (established by bilateral common carotid artery ligation), and IL-1ß group (treated by IL-1ß monoclonal antibody intracerebroventricular injection on based on model group). Rat learning ability was evaluated by Morris water maze assay. IL-1ß expression in brain tissue and peripheral blood was examined by using Real Time-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Hippocampus apoptosis was detected by caspase 3 activity detection kit. B-cell lymphoma-2 (Bcl-2) and p38 mitogen-activated protein kinase (MAPK) protein levels were assessed by Western blot assay. RESULTS: IL-1ß expression was increased, caspase 3 activity was enhanced, Bcl-2 level was declined, and p-P38 phosphorylation was elevated in brain tissue and peripheral blood from VD model group compared to sham group (p<0.05). IL-1ß monoclonal antibody significantly reduced IL-1ß expression, improved learning ability, attenuated caspase 3 activity, increased Bcl-2 level, and declined p-P38 expression in VD rats compared to model group (p<0.05). CONCLUSIONS: IL-1ß can delay VD occurrence and development through the P38-MAPK signaling pathway to regulate cell apoptosis and improve learning ability.

Upregulation of serum miR-103 predicts unfavorable prognosis in patients with colorectal cancer.

OBJECTIVE: Circulating microRNAs (miRNAs) have been reported as biomarkers for the early detection of colorectal cancer (CRC). We aimed at evaluating the diagnostic and prognostic value of serum miR-103 in CRC patients. PATIENTS AND METHODS: Quantitative reverse-transcription PCR (qRT-PCR) was applied to measure the miR-103 levels in blood samples of 96 patients and 60 controls. RESULTS: Our results demonstrated that serum miR-103 was overexpressed in CRC subjects and the receiver operating characteristic (ROC) curve analysis showed that serum miR-103 could differentiate CRC cases from controls with relatively high accuracy. In addition, serum miR-103 level was more frequently detected in CRC patients with positive lymph node metastasis, distant metastasis and advanced tumor stage. Moreover, serum miR-103 levels in 23 postoperative blood samples were lower than paired preoperative plasma specimens, and serum miR-103 levels were re-elevated in seven patients at recurrence. Furthermore, serum miR-103 was significantly correlated with worse clinical factors, as well as poorer recurrence-free survival or overall survival. Finally, multivariate analysis confirmed that serum miR-103 was an independent prognostic marker for CRC. CONCLUSIONS: Taken together, serum miR-103 might be a promising biomarker for diagnosis and prognosis of CRC.

[The combined interpretation schemes including VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma].

Objective:To compare the performances of VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma, and find the most appropriate combined interpretation scheme. Method:The current study included a total of 346 subjects. Ninety-six subjects were nasopharyngeal carcinoma cases which were pathologically verified by the biopsy under electronic laryngoscope. The remaining 250 subjects, who received EBV tests at the same period, were normal healthy individuals without nasopharyngeal carcinoma. VCA-IgA, EA-IgA and Rta-IgG were detected in all cases. The clinial data were analyzed retrospectively. Result:Best cutoff points of VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma were 1.37 s/co, 0.706 s/co and 0.817 s/co; the sensitivities were 88.5%,49.0% and 65.6%; the specificities were 88.8%,96.0% and 95.2%, respectively. The diagnostic accuracy of VCA-IgA was significantly higher than that of EA-IgA and Rta-IgG (P<0.05). Three combined interpretation schemes were developed based on the VCA-IgA: ①VCA-IgA+EA-IgA; ②VCA-IgA+Rta-IgG; ③VCA-IgA+EA-IgA+Rta-IgG. Compared to the VCA-IgA, all the combined interpretation schemes had increased sensitivities and decreased specificities. The scheme 3 had the highest sensitivity. And the scheme 2 had the highest Youden index, and a comparable diagnosis accuracy to that of VCA-IgA (P>0.05). Conclusion:VCA-IgA, EA-IgA and Rta-IgG were all helpful indicators in the diagnosis of nasopharyngeal carcinoma. VCA-IgA was more accurate than the EA-IgA and Rta-IgG. Combined interpretation schemes were helpful in improving the sensitivity. Because the clinical symptoms of nasopharyngeal carcinoma are often insidious and the missed diagnosis by serological examination may lead to serious consequences. It is of clinical value to adopt the combined interpretation schemes to improve the diagnostic sensitivity of nasopharyngeal carcinoma.