Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma

AIM To determine whether the number of examined lymph nodes(LNs) is correlated with the overall survival of gallbladder carcinoma(GBC) patients. METHODS Patients were collected from the Surveillance Epidemiology and End Results database(2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a KaplanMeier analysis. The log-rank test was used for univariate comparisons.RESULTS In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage Ⅰ and Ⅱ disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage Ⅰ, four or five for stage Ⅱ, and six for stage ⅢA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria.CONCLUSION The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.

Efficacy of Topical versus Oral 5-Aminosalicylate for Treatment of 2,4,6-Trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis in Rats

5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

Outcomes and prognostic factors of patients with stage? ⅠB and? ⅡA pancreatic cancer according to the 8^(th) edition American Joint Committee on Cancer criteria

AIM To evaluate the changes in the 8^(th) edition American Joint Committee on Cancer(AJCC) for defining stage?ⅠB and?ⅡA pancreatic cancer and identify their prognostic factors.METHODS Pancreatic cancer patients were selected from the Surveillance Epidemiology and End Results database(1973-2013). The enrolled patients were divided into?ⅠB and?ⅡA groups based on tumor size according to the 8^(th) edition AJCC criteria. Clinical characteristics, including age, gender, race, tumor size, primary site, and grade were summarized. Univariate and multivariate analyses were performed to explore the prognostic factors of the?ⅠB and?ⅡA stages of pancreatic cancer under new criteria.RESULTS A total of 1349 pancreatic cancer patients were included. More patients had stage?ⅠB rather than stage?ⅡA. Stage?ⅠB tumors(54.85%) were mainly located in the head of the pancreas, while stage?ⅡA tumors were more often located in the tail and head of the pancreas(35.21% and 31.75%, respectively). The survival time of stage?ⅠB and?ⅡA patients had no significant difference. Univariate and multivariate analyses indicated that the prognostic factors of survival for stage?ⅠB and?ⅡA patients were different. for stage?ⅠB patients, age and primary site were the independent prognostic factors; for stage?ⅡA patients, age and grade were the independent prognostic factors. The risk of death was lower among patients aged ≤ 65 years than those aged > 65 years.CONCLUSION The prognostic factors for stage?ⅠB and?ⅡA patients are different, but age is the independent prognostic factor for all patients. The survival time of stage?ⅠB and?ⅡA patients has no significant difference.

Profiles of metabolic gene expression in the white adipose tissue, liver and hypothalamus in leptin knockout(Lep^(△I14/△I14)) rats

Leptin deficiency is principally linked to metabolic disorders. Leptin knockout（Lep△I14/△I14 Sprague Dawley rats created by CRISPR/Cas9 is a new model to study metabolic disorders. We used a whole rat genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of the white adipose tissue, liver and hypothalamus in Lep△I14/△I14）and wild-type（WT） rats. We found 1,651 differentially expressed（enriched） genes in white adipose tissue,916 in the liver, and 306 in the hypothalamus in the Lep△I14/△I14 rats compared to WT. Gene ontology category and KEGG pathway analysis of the relationships among differentially expressed genes showed that these genes were represented in a variety of functional categories, including fatty acid metabolism, molecular transducers and cellular processes. The reliability of the data obtained from microarray was verified by quantitative real-time PCR on 14 representative genes. These data will contribute to a greater understanding of different metabolic disorders, such as obesity and diabetes.

Comparable outcomes but higher risks of prolonged viral RNA shedding duration and secondary infection in cancer survivors with COVID-19: A multi-center, matched retrospective cohort study

Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-cancer patient cohort were 64.0(55.0–73.0)and 64.0(54.0–73.5),respectively(P=0.909).Cancer survivors reported a higher incidence of symptom onset than non-cancer patients.Fever(80.3%vs.65.0%;P=0.026)was the most prevalent symptom,followed by cough(65.6%vs.37.7%;P<0.001),myalgia,and fatigue(45.9%vs.13.6%;P<0.001).The risks of the development of severe events(adjusted hazard ratio[AHR]=1.25;95%confidence interval[CI]:0.76–2.06;P=0.378)and mortality(relative risk[RR]=0.90,95%CI:0.79–1.04;P=0.416)in the cancer survivor cohort were comparable to those of the matched non-cancer patient cohort.However,the cancer survivor cohort showed a higher incidence of secondary infection(52.5%vs.30.1%;RR=1.47,95%CI:1.11–1.95;P=0.002)and a prolonged viral RNA shedding duration(32 days[IQR 26.0–46.0]vs.24.0 days[IQR 18.0–33.0];AHR=0.54;95%CI:0.38–0.80;P<0.05).Conclusion Compared to non-cancer patients,cancer survivors with COVID-19 exhibited a higher incidence of secondary infection,a prolonged period of viral shedding,but comparable risks of the development of severe events and mortality.It is helpful for clinicians to take tailored measures to treat cancer survivors with COVID-19.

Effect of a Hybrid Micro/Nano-integrated Titanium Surface on Behavior of Rat Osteoblasts

The objective of this study was to investigate the effect of a new combined micro/nanoscale implant surface feature on osteoblasts＇ behaviors including cell morphology, adhesion, proliferation, differentiation, and mineralization in vitro. A new micro/nano-hybrid topography surface was fabricated on commercial pure titanium（Cp Ti） by a two-step sandblasted acid-etching and subsequent alkali-and heattreatment（SA-AH）. The conventional sandblasted/acid-etching（SA） treatment and alkali and heat（AH） treatment were also carried out on the Cp Ti as controls. Surface microstructures of the Ti disc samples were assessed by scanning electron microscopy（SEM）. The neonatal rat calvaria-derived osteoblasts were seeded on these discs and the initial cell morphology was evaluated by SEM and immunofluorescence. Initial adhesion of the cells was then assayed by DAPI staining at 1, 2, and 4 h after seeding. The Cell Counting Kit-8（CCact K8） assay, gene expression of osteoblastic markers（ALP, Col 1, OCN, BSP, OSX, Cbfα1） and Alizarin Red S staining assays were monitored respectively for cell proliferations, differentiation and mineralization. The results show significant differences in osteoblast＇s behaviors on the four kinds of Ti surfaces. Compared with Cp Ti surface, the SA and AH treatment can significantly promote cell adhesion, differentiation and mineralization of osteoblasts. In particular, the combined SA and AH treatments exhibit synergistic effects in comparison with the treatment of SA and AH individually, and are more favorable for stimulating a series of osteogenous responses from cell adhesion to mineralization of osteoblasts. In summary, this study provides some new evidence that the integrated micro/nanostructure on the Cp Ti surface may promote bone osseointegration between the Ti implantbone interfaces in vitro.

Zinc protoporphyrin IX enhances chemotherapeutic response of hepatoma cells to cisplatin

AIM:To investigate the effect of zinc protoporphyrin IX on the response of hepatoma cells to cisplatin and the possible mechanism involved.METHODS:Cytotoxicity was determined using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was determined by a flow cytometric assay.Western blotting was used to measure protein expression.Heme oxygenase(HO)-1 activity was measured by determining the level of bilirubin generated in isolated microsomes.Reactive oxygen species(ROS)production was monitored by flow cytometry.Caspase-3 activity was measured with a colorimetric assay kit.Mice were inoculated with 1×107 tumor cells subcutaneously into the right flanks.All mice were sacrificed 6 wk after the first treatment and tumors were weighed and measured.RESULTS:Overexpression of HO-1 in HepG2 cell line was associated with increased chemoresistance to cisdiaminedichloroplatinum(cisplatin;CDDP)compared to other cell lines in vitro.Inhibition of HO-1 expression or activity by zinc protoporphyrin IX(ZnPP IX)markedly augmented CDDP-mediated cytotoxicity towards all liver cancer cell lines in vitro and in vivo.In contrast,induction of HO-1 with hemin increased resistance of tumor cells to CDDP-mediated cytotoxicity in vitro and in vivo.Furthermore,cells treated with ZnPP IX plus CDDP exhibited marked production of intracellular ROS and caspase-3 activity,which paralleled the incidence of cell apoptosis,whereas hemin decreased cellular ROS and caspase-3 activity induced by CDDP.CONCLUSION:ZnPP IX increases cellular sensitivity and susceptibility of liver cancer cell lines to CDDP and this may represent a mechanism of increasing ROS.

Effect of Homoharringtonine on Bone Morrow CD34^+CD7^+ Cells in Chronic Granulocytic Leukemia

Objective： To explore the effect of homoharringtonine （HHT） on bone morrow CD34^＋CD7^＋ cells in chronic granulocytic leukemia （CGL）. Methods： The changes of bone morrow CD34^＋CD7^＋ cells were observed after the treatment of HHT in 23 cases with CGL. The proliferation and apoptosis of CD34^＋CD7^＋ cells treated with HHT in vitro were studied. Results： The proportion of CD34^＋CD7^＋ cells in CGL （0.145±0.021） was higher than that of normal control （0.052±0.013）. The proportion of CD34^＋CD7^＋ cells in patients who got cytogenetic responses to HHT （0.072±0.020） decreased remarkably, but not in those patients who did not got cytogenetic responses to HHT, （0.137±0.023）. the proliferation of CD34^＋ cells was inhibited and the proportion of CD34^＋CD7^＋ cells decreased after cultured with HHT （0.134 in 24 h, 0.126 in 48 h and 0.102 in 72）. The apoptosis rate of CD34^＋CD7^＋ cells was higher than that in CD34^＋CDT cells （35.39%±4.39% versus 24.57%±4.01%, P〈0.05） 72 h after culture with HHT. Conclusion： The proportion of CD34^＋CD7^＋ cells in CGL was higher than that of normal control and HHT may inhibit the proliferation and induce apoptosis of bone marrow CD34^＋CD7^＋ cells.

Effect of Phosphorus-32 Glass Microspheres on the Human Hepatocellular Carcinoma in Nude Mice

Objective To study anticancer effect and ultrastructural influence of phosphorus 32 glass microspheres( 32 P GMS) injected in the hepatocellular carcinoma in nude mice. MethodsThe ultrastructural changes of tumor in both the treatment group and control group were examined by transmission electron microscope. ResultsIn the treatment group,a large number of tumor cells were killed and the death rate of tumor cells was much higher(35%-70%). Ultrastructurally, severe nuclear damage was observed in the dead cells. The early characteristics of necrosis such as margination of heterochromatin were also found in some tumor cells. Besides,well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. The skin and muscle close to the tumor were normal. In the control group,the tumor consisted of poor differentiated tumor cells,in which there were only a few appototic cells(5%). ConclusionThe results suggest that the local administration of 32 P GMS produces obviously the anticancer effect.

A Study on the Ultrastructure and Gene Location of Hereditary Gingival Fibromatosis

Objective\ To ascertain the histological characteristics of hereditary gingival fibromatosis and the location of HGF gene. Methods\ A pedigree analysis of HGF was made. The ultrastructure of gingival overgrown tissue was observed by electron microscopy (EMS) and the location of the HGF gene defined with microsatellite markers. Results\ The HGF consisted of coarse collagen bundles and fibrocytes, epithelial cells, smooth muscle cells, etc. were abnormally arranged; the HGF locus had been mapped to chromosome 5q13 q22. Conclusion\ The gingival pathological changes resemble 'hamartoma' and the findings have implications for identification of the underlying genetic basis of HGF.

Effects of suspension laparoscopy and pneumoperitoneum laparoscopic surgery on ovarian function, inflammatory response and stress hormone in patients with ovarian cystectomy

Objective:To investigate the effects of suspension laparoscopy and pneumoperitoneum laparoscopic surgery on inflammatory response, stress hormone and ovarian function in patients with ovarian cystectomy.Methods: Retrospective analysis of the data of laparoscopic ovarian cyst denudation in our hospital from July 2015 to August 2017, and they were were divided into the control group and the treatment group according to the surgical methods they accepted. The levels of inflammatory factors and stress hormone preoperative and postoperative 24 h, and ovarian function of the menstrual period 3rd day preoperative and postoperative 3 months of the two groups were compared.Results: There was no significant difference in the levels of TNF-α, CRP, COR, NE, E2, LH and FSH between the two groups before the operation. Postoperative 24 h, the levels of TNF-α, CRP, COR and NE in the treatment group were significantly lower than those in the control group, and the level of E2 in the treatment group was higher than that in control group, the levels of LH and FSH in the treatment group were lower than those in control group postoperative 3 months, the difference were statistically significant.Conclusion: Compared with pneumoperitoneum laparoscopic surgery, suspended laparoscopic surgery can effectively reduce the inflammatory response, reduce the level of stress hormone and improve ovarian function in patients undergoing ovarian cystectomy, which has a certain clinical value.

Spatial learning and memory deficits in young adult mice exposed to a brief intense noise at postnatal age

Noise pollution is a major hazardous factor to human health and is likely harmful for vulnerable groups such as pre-term infants under lifesupport system in an intensive care unit. Previous studies have suggested that noise exposure impairs children’s learning ability and cognitive performance and cognitive functions in animal models in which the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. The potential role of noise induced hearing loss(NIHL), rather than the oxidant stress, has also been indicated by a depression of neurogenesis in the hippocampus long after a brief noise exposure, which produces only a tentative oxidant stress. It is not clear if noise exposure and NIHL during early development exerts a long term impact on cognitive function and neurogenesis towards adulthood. In the present study, a brief noise exposure at high sound level was performed in neonatal C57BL/6J mice(15 days after birth) to produce a significant amount of permanent hearing loss as proved 2 months after the noise. At this age, the noise-exposed animals showed deteriorated spatial learning and memory abilities and a reduction of hippocampal neurogenesis as compared with the control. The averaged hearing threshold was found to be strongly correlated with the scores for spatial learning and memory. We consider the effects observed are largely due to the loss of hearing sensitivity, rather than the oxidant stress, due to the long interval between noise exposure and the observations.

Stage Ⅲ should be subclassified into Stage ⅢA and ⅢB in the American Joint Committee on Cancer(8^(th) Edition) staging system for pancreatic cancer

AIM To ascertain the prognostic role of the T4 and N2 category in stage Ⅲ pancreatic cancer according to the 8 th edition of the American Joint Committee on Cancer(AJCC) classification.METHODS Patients were collected from the Surveillance Epidemiology and End Results(SEER) database(2004-2013) and were divided into three groups: T(1-3)N2, T4 N(0-1), and T4 N2. Overall survival(OS) and disease-specific survival(DSS) of patients were evaluated by the Kaplan-Meier method. RESULTS For the first time, we found a significant difference in OS and DSS between T(1-3)N2/T4 N(0-1) and T4 N2 butnot between T(1-3)N2 and T4 N(0-1). A higher grading correlated with a worse prognosis in the T(1-3)N2 and T4 N2 groups.CONCLUSION Patients with stage T4 N2 had a worse prognosis than those with stage T(1-3)N2/T4 N(0-1) in the 8 th edition AJCC staging system for pancreatic cancer. We recommend that stage Ⅲ should be subclassified into stage ⅢA [T(1-3)N2/T4 N(0-1)] and stage ⅢB(T4 N2).

Metabolic disorders of fatty acids and fatty acid amides associated with human gastric cancer morbidity

Background Gastric cancer （GC） is one of the most common types of cancer in the world. A change in the metabolism of lipids in tumor cells could lead to the pathogenesis of cancer. In this study, we investigated fatty acid and fatty acid amide metabolic perturbations associated with GC morbidity.

High-frequency Noise-induced Hearing Loss Disrupts Functional Connectivity in Non-auditory Areas with Cognitive Disturbances

Dear Editor,Approximately 500 million individuals suffer from hearing loss worldwide. The number of hearing-impaired individuals is estimated to increase to 900 million by 2050. The etiology of hearing loss is complex.

LncRNA HCP5-encoded protein contributes to adriamycin resistance through ERK/mTOR pathway-mediated autophagy in breast cancer cells

Adriamycin(ADR),also known as doxorubicin,is an anthracycline anticancer drug and a chemotherapeutic drug commonly used in breast cancer treatments.1 However,breast cancer patients can gradually become tolerant to chemotherapy.Therefore,improving the curative effect of ADR remains an urgent problem to be solved.Autophagy is a complex catabolic process;normal living cells break down damaged organelles or aggregated molecules and absorb energy to maintain homeostasis through autophagy.