Objective This study aimed at observing expression and clinical significance of metadherin in gastric adenocarcinoma and exploring the potentially regulating mechanism of metadherin in invation and migration of gastric cancer.Methods Expressions of metadherin and E-cadherin in primay lesion of gastric cancer were detected by immunohistochemistry and their correlation to clinicopathologic characteristics and prognosis were analyzed by Chi-square tests.Transwell assay and wound healing assay were applied for the ability of invasion and metastasis in gastric cancer cells.Then,the down-regulatied metadherin expression in MKN45 cells by RNA interference (siRNA) was carried out and furthermore,the regulation role of metadherin in epithelial-mesenchymal transition was analyzed also in invasion and migration of gastric cancer cells.Results The positive expression of metadherin was correlated to invading depth (P =0.029),lymph node metastasis (P =0.001),TNM stage (P =0.014) and inhibiting E-cadherin expression (P =0.001).The patients with positive metabherin shared poorer prognosis.Furthermore,the down-regulated metabherin in MKN45 cells would result in the increasing expression of E-cadherin,as well as decreasing expression of N-eadherin,Slug and Snail.At the same time,the abilities of invasion (P =0.027) and migration (P =0.008) of MKN45 cells was decreased.Conclusion metabherin induces EMT in metastasis of gastric adenocarcinoma via activating either Slug or Snail but not twist,which would result in the poorer prognosis.

OBJECTIVE Toobservetheeffectoftemozolomide(TMZ)incombinationwithtetran-drine(TET)on cell viability,colony formation,migration and cell apoptosis of human glioblastoma U87 cells.METHODS TheviabilityofU87cellstreatedwithTET(8-64μmol·L-1),TMZ(50-400 μmol·L-1 )and TMZ combined with TET (3.2,6.4 μmol·L-1 )was detected by cytotoxicity assays with Cell Counting Kit-8 (CCK-8),the colony formation was detected by Giemsa staining,cell migration ability was detected by Transwell migration assay,cell apoptosis was assayed by flow cytometry using Annexin Ⅴ /PI double staining,and the expression of apoptosis-related proteins expression was detec-tedbyWesternblotting.RESULTS ThedataofCCK-8showedthatTET(r=0.903,P<0.05)orTMZ (r=0.995,P<0.05)could inhibit U87 cell viability alone in a concentration-dependent manner.The cell viability inhibition rate of U87 cells by TMZ co mbined with TET was higher than by TMZ or TET alone. Data showed that the effect of TMZ combined with TET was additive.TMZ 100 μmol·L-1 inhibited U87 cell colony formation and migration ablility compared with normal control.The inhibition rate of U87 cells by TMZ 100 μmol·L-1 combined with TET (3.2 and 6.4 μmol·L-1 )was more significant than by TMZ alone (P<0.05).Compared with TMZ alone,TMZ combined with TET (3.2 and 6.4 μmol·L-1 )signifi-cantly down-regulated the expression of anti-apoptotic protein Bcl-XL,but significantly up-regulated the expression of cleaved caspase 3 protein and cleaved poly(ADP-ribose)polymerase.CONCLUSION TET combined with TMZ can inhibit U87 cell viability,colony formation and migration by activating caspase-dependent apoptotic pathway,resulting in apoptosis.

Objective:To investigate the level of suicide ideation of female nurses in the public grade A hospitals of Fujian Province, and to explore the influence of impulsive personality and social support on the suicidal ideation of nurses.Methods:A total of 1 000 female nurses from a number of public grade A hospitals in Fujian Province were investigated by convenient sampling method from March to October 2019, using Barratt impulsive personality scale, social support scale and suicide ideation scale were used for the survey.Results:The prevenlence of suicidal ideation was 9.74%. Social support was negatively correlated with impulsive personality and suicidal ideation, and impulsive personality was positively correlated with suicidal ideation ( r=-0.329, -0.449, 0.291, P<0.01). The social support had an indirect mediating effect on the influence of impulsive personality on suicidal ideation. Conclusions:Nursing managers can promote the level of social support of nurses and reduce the intensity of suicidal ideation.

MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.
Animals ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; therapy ; Down-Regulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; HEK293 Cells ; Humans ; Male ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs ; genetics ; Middle Aged ; Neoplasm Invasiveness ; RNA Interference ; Receptor, Notch1 ; genetics ; metabolism ; Receptors, Autocrine Motility Factor ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Survival Analysis ; Xenograft Model Antitumor Assays

Objective:To explore the effects and possible mechanisms of melatonin combined with enriched environment on the learning and memory ability of senescence-accelerated mouse prone 8(SAMP8).Methods:Forty-eight SAMP8 male mice aged 4 months were randomly divided into model group, enriched environment group, melatonin group and melatonin combined with enriched environment group (combined intervention group) by random number table method, with 12 mice in each group. Mice in the melatonin group and combined intervention group were subcutaneously injected with melatonin at a dose of 8 mg·kg -1·d -1, and the mice in the model group and the enriched environment group were given the same amount of normal saline instead.The mice in model group and melatonin group were raised in a standard environment, and the mice in enriched environment group and combined intervention group were raised in an enriched environment.The intervention lasted 28 days. The aging degree of mice was scored before and 28 days after the intervention. Morris water maze test was used to detect the learning and memory ability of mice. Nissl staining and TUNEL staining were used to observe the Nissl staining positive cells and apoptotic cells in the CA1 area of hippocampus.ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus of mice. Western blot was used to detect the levels of amyloid β-protein (Aβ) 1-42, microtubule-associated protein tau (tau) phosphorylated at threonine (Thr) 205 (Tau pT205), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) p65 protein in the hippocampus of mice. qRT-PCR was used to detect the levels of TLR4, NF-κB p65 mRNA in the hippocampus of mice. SPSS 22. 0 statistical software was used for repeated measure ANOVA, one-way ANOVA and LSD test. Results:(1) Aging score: after intervention, the aging scores of mice in the four groups were significantly different ( F=120.601, P<0.01). The aging scores of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group (all P<0.05), while the aging score of mice in the combined intervention group was significantly lower than those in the enriched environment group and melatonin group (both P<0.05). (2) The results of the location navigation experiment showed that the time × group interaction effect of the escape latencies of mice in the four groups were significant ( F=30.524, P<0.001). From the 2nd to 4th day, the escape latencies of mice in the enriched environment group, melatonin group and combined intervention group were all lower than that in the model group (all P<0.05). The results of the space exploration experiment showed that the residence time in the target quadrant and the number of platform crossings of mice in the four groups were significantly different ( F=291.328, 113.482, both P<0.01). The residence time in the target quadrant ((29.45±1.70)s, (32.44±1.55)s, (37.48±0.84) s) and the number of platform crossings ((6.44±0.61) times, (7.16±0.70) times, (12.60±1.23) times) of mice in the enriched environment group, melatonin group and combined intervention group were higher than those in the model group ((15.07±1.28) s, (4.10±0.61) times), while the residence time in the target quadrant and the number of platform crossings of mice in the enriched environment group and the melatonin group were significantly lower than those in the combined intervention group (all P<0.05). (3) Nissl and TUNEL staining showed that the number of Nissl positive neurons in the hippocampal CA1 region of mice in the four groups were significantly different ( F=809.264, P<0.01), and the number of apoptotic cells in the hippocampal CA1 region were also significantly different ( F=1 060.583, P<0.01). The number of Nissl stained positive neurons in the hippocampal CA1 region of mice in the combined intervention group was more than those in the model group, enriched environment group, and melatonin group (all P<0.05), and the number of apoptotic cells were less than those in the model group, enriched environment group, and melatonin group (all P<0.05). (4) The results of ELISA assay showed that there were significantly different in the levels of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the four groups ( F=152.887, 63.506, 432.026, all P<0.01). The contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group(all P<0.05). Among them, the contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (5) Western blot analysis showed that there were significantly different in the protein expression levels of Aβ1~42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the four groups ( F=122.349, 98.934, 201.635, 116.553, all P<0.01). The protein expression levels of Aβ1-42, tau pT205, TLR4, and NF-κB p65 in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group.Among them, the protein expression levels of Aβ1-42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (6) qRT-PCR showed that the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the four groups were significantly different ( F=42.913, 102.446, both P<0.01). The mRNA expression levels of TLR4 ((0.63±0.05), (0.55±0.04), (0.42±0.03)) and NF-κB p65 ((0.98±0.06), (0.82±0.04), (0.72±0.04)) in the hippocampus of mice in the enriched environment group, melatonin group and combined intervention group were lower than those in the model group ((0.74±0.07), (1.20±0.05)) (all P<0.05). Among them, the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). Conclusion:Melatonin combined with enriched environment can improve the learning and memory ability and neuroinflammatory response of SAMP8 mice, and its mechanism may be related with the down-regulation of TLR4/NF-κB p65 signaling pathway.

Objective:To investigate the prognostic significance of tumor architecture in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Methods:A retrospective study was performed on 958 patients who underwent nephroureterectomy in Second Affiliated Hospital of Zhejiang university (156) and Renji Hospital (802) between January 1998 and June 2019. There were 630 males and 328 females with median age 67 years old, ranging 30-89 years old. Among them, 499 patients suffered with preoperative hydronephrosis, 370 patients suffered with hypertension, 120 patients suffered with diabetes, 252 patients had history of smoking and 119 patients had history of non-muscle invasive bladder cancer (NMIBC) or with NMIBC. 489 patients had tumor in renal pelvic, 394 patients had tumor in ureter and 75 patients had tumor in both sites. Laparoscopic surgery was performed in 543 patients while open surgery was performed in 415 patients. The χ 2 test was used to detect the association between tumor architecture and several clinicopathological features. Kaplan-Meier method with the log-rank test was used to assess survival analysis. Multivariate analyses were conducted using Cox proportional-hazards regression model. Results:516 cases (53.9%) showed papillary architecture(Group A) and 442 cases (46.1%) showed sessile architecture(Group B). 543 patients had a tumor ≤3 cm and 415 had a tumor >3 cm. Low pathological grade and high grade was diagnosed in 275 and 683 patients, respectively. The distribution of pathological stage was pT a-1 in 441 cases, pT 2 in 180 cases, pT 3 in 308 cases and pT 4 in 29 cases. Lymphadenectomy was performed in 227 patients and 62 patients were pathologically confirmed lymph node metastasis. 48 patients were found squamous or glandular differentiation. Lymphovascular invasion (LVI) was observed in 150 patients. 134 patients were multifocality. Positive surgical margin was found in 43 patients. Median follow-up was 39 (ranging, 2-206) months. During follow-up, a total of 304 patients died and 236 died of UTUC. 5-year OS and CSS were 76.6% and 81.8%, respectively, in patients with papillary architecture (group A), which were significantly higher than 54.4% and 60.5% in patients with sessile architecture (group B, all P<0.001). Patients in group B had more female patients (38.9% vs.30.3%, P=0.005), ureteral location (47.1% vs. 36.1, P=0.002), hydronephrosis (55.9% vs.48.8%, P=0.030) and postoperative adjuvant chemotherapy (27.1% vs. 14.7%, P<0.001), higher pathological grade (89.6% vs.55.6%, P<0.001) and stage (79.4% vs.32.4%, P<0.001), lymph node metastasis rate (12.0% vs.1.7%, P<0.001), squamous or glandular differentiation (9.5% vs.1.2%, P<0.001) and LVI (24.4% vs.8.1%, P<0.001) than patients in group A. Cox multivariate regression analysis showed that sessile architecture ( P=0.022, 0.028), age ≥65 years ( P<0.001, <0.001), history of diabetes ( P=0.008, 0.043), history of NMIBC or with NMIBC ( P<0.001, <0.001), higher grade ( P=0.002, <0.001), advanced tumor stage ( P=0.003, 0.005), lymph node metastasis ( P=0.003, 0.044), squamous or glandular differentiation ( P=0.008, 0.027) and positive surgical margin ( P=0.003, 0.010) were independent risk factors for OS and CSS. However, tumor >3 cm ( P=0.013, 0.131) and positive LVI ( P=0.045, 0.174) were independent risk factors for CSS rather than OS. Conclusions:UTUC is high malignancy. Tumor architecture was one of an independent risk factor for OS and CSS in UTUC patients and sessile tumors were more malignant, more aggressive and have worse prognosis.

Objective To understand the effects of different water iodine level on iodine nutrition and thyroid function in pregnant women,and provide a reference for prevention and treatment of iodine deficiency disorders in the future.Methods According to the background material of water iodine in provinces given non-iodized salt,the administrative villages with water iodine content ＜ 10,10-49,50-99,100-299 and ≥ 300 μg/L were selected as survey sites in Shandong,Shanxi,Hebei,Henan,Jiangsu and Anhui provinces.Urine,blood,drinking water and salt samples were collected from pregnant women at the site of investigation,and urinary iodine,serum iodine,thyroid function and antibody index,water iodine,and salt iodine were measured;thyroid volume was also examined.Results A total of 575 pregnant women were investigated.The medians urinary iodine of pregnant women with water iodine ＜ 10,10-49,50-99,100-299 and ≥300 μg/L groups were 175.55,180.90,139.70,330.15 and 817.70 μg/L,respectively,and the differences were statistically significant in different water iodine groups (H =152.593,P ＜ 0.01).The levels of serum iodine and free thyroxine (FT4) were significantly different among pregnant women in different water iodine groups (H =82.843,F =3.070,P ＜ 0.01 or ＜ 0.05).However,there was no significant difference in serum thyroid stimulating hormone (TSH) levels (H =1.774,P ＞ 0.05).And with the increase of water iodine levels,the abnormal rate of TSH showed the phenomenon of middle low and both ends high ("U" type,x2 =16.729,P ＜ 0.01).There were no significant differences in the positive rates of serum thyroid peroxidase antibody (TPOAb),thyroglobulin antibody (TgAb),any antibody and double antibodies in pregnant women among different water iodine groups (P ＞ 0.05).And there was a statistically significant difference in the detection rate of subclinical hypothyroidism (x2 =11.869,P ＜ 0.05).The rates of goiter in pregnant women among different water iodine groups were less than 5％.The difference in detection rates of thyroid nodules was statistically significant (x2 =13.591,P ＜ 0.05),and the rate was the highest in water iodine ≥300 μg/L group (21.33％,16/75).Conclusions In water iodine ≥300 μg/L group,urinary iodine level of pregnant women is in the level of iodine excess,and serum iodine level,FT4 level,thyroid nodules detection rate are higher.The abnormal rate of serum TSH and the detection rate of hypothyroidism show a "U" curve that increases at iodine deficiency and iodine excess.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.