AIM: To study the role of c-Jun NH_2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-α (TNF-α) or H_2O_2 in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125, then exposed to 1 nmol/L of TNF-α or micromolar H_2O_2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS: Compared to control adipocytes, 12 h incubation with TNF-α or H_2O_2 led to 50%-55% reduction (P<0.01) of the insulin-dependent glucose uptake. JNK1 siRNA transfection significantly inhibited JNK1 expression and blocked the TNF-α or H_2O_2-induced impairments of cellular glucose uptake. Pretreatment with SP600125 (20 μmol/L) resulted in significant increases in insulin-stimulated glucose uptakes in both TNF-α (66%) and H_2O_2 (62%) treated adipocytes (P<0.01). CONCLUSION: JNK plays a key role in TNF-α or H_2O_2 induced insulin resistance in 3T3-L1 adipocytes, and inhibition of JNK over-activation may be a new therapeutic target for insulin resistance.

AIM:To study the role of c-Jun NH2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-? (TNF-?) or H2O2 in 3T3-L1 adipocytes. METHODS:Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125,then exposed to 1 nmol/L of TNF-? or micromolar H2O2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS:Compared to control adipocytes,12 h incubation with TNF-? or H2O2 led to 50%-55% reduction (P

AIM:To investigate the role of high glucose in primary hepatocytes of mice fed with a high fat di-et.METHODS:Male C57BL/6J mice were fed a high fat (45%of calories) diet ad libitum for 6 weeks to induce hepatic steatosis.Primary hepatocytes were isolated from the mouse liver by the 2 step collagenase perfusion method .The cells were incubated in low glucose ( 5 mmol/L ) , low glucose plus mannitol ( 30 mmol/L ) , or high glucose ( 35 mmol/L ) DMEM medium for 12 h.The cell viability , apoptosis , mitochondrial membrane potential , and caspase enzymatic activities were measured.Furthermore, proteins related to the stress-sensitive signaling pathway of regulating high glucose-induced apoptosis in primary hepatocytes were determined by Western blotting .RESULTS:Incubation with 35 mmol/L glucose re-sulted in a significant decrease in cell viability and an increase in apoptosis , whereas mannitol had no significant effect on the cell viability or apoptosis .A progressive depolarization of the mitochondria , an increase in cytosol cytochrome C and a dramatic decrease in mitochondrial cytochrome C in high-glucose stressed hepatocytes were observed .The enzymatic activi-ties of caspase-9 and caspase-3, but not caspase-8, were significantly increased in high glucose-stressed hepatocytes ( P<0.05).High glucose treatment suppressed the expression of Bcl-2 and Bcl-xL, while it increased the expression of the pro-apoptotic factor Bax .CONCLUSION:High glucose stress reduces mitochondrial membrane potential , initiates mitochon-dria-mediated apoptotic pathways and promotes apoptosis of hepatocytes with steatosis .This may be an important pathologi-cal mechanism of hyperglycemia-induced progression of nonalcoholic fatty liver disease .

Objective: To investigate psychological and behavioral responses and the prevalence of acute stress disorder (ASD) among the injured from a serious road traffic accident. Methods: The injured persons at ages of 7 years and older from a serious road traffic accident were enrolled, and individuals with severe injury were exclude. Participants' gender, age, educational level, marital status, injury severity, family member's injury and death during the accident and psychological and behavioral status were collected. The prevalence of ASD was estimated using a semi-structured interview and the ASD Scale, and the factors affecting the development of ASD were identified using a multivariable logistic regression model. Results: A total of 132 survivors participated in psychological crisis assessment, including 82 men (62.12%) and 50 women (37.88%) and with a mean age of (46.50±18.57) years. There were 6 participants without obvious trauma (4.54%), 113 with mild injury (85.61%) and 13 with moderate injury (9.85%), and there were 6 participants with death of their family members during this accident. Insomnia, anxiety, flashback and fear were predominant psychological and behavioral responses, with prevalence rates of 42.42%, 35.58%, 26.52% and 23.48%, respectively. The prevalence of ASD was 30.30% among participants, and a higher rate of ASD was detected among women than among men (52.00% vs. 17.07%; χ2=17.940, P<0.001). The detection of ASD was higher among participants with death of their family members than among those without death of their family members (83.33% vs. 26.98%; χ2=8.370, P=0.004), and a higher detection rate of ASD was seen among participants with moderate injury (61.54%; χ2=6.786, P=0.034). Multivariable logistic regression analysis showed a higher risk of ASD among females (OR=7.764, 95%CI: 3.187-18.915) and those with a high educational level (high school/technical secondary school, OR=6.896, 95%CI: 1.030-46.152; diploma and above, OR=71.583, 95%CI: 4.145-1 236.270). Conclusions Insomnia and anxiety are predominant psychological and behavioral responses following serious road traffic accidents, and women and individuals with a high educational level present a high risk of ASD, which requires to be given timely psychological crisis interventions.

OBJECTIVE To study the audiological and etiological characteristics of infants failed to pass hearing screening. METHODS 126 infants received audiological diagnostic tests,including auditory brainstem response(ABR),40 Hz auditory event related potential(40 Hz AERP),distortion product otoacoustic emissions(DPOAE),tympanometry and acoustic reflex. The degrees and types of the hearing loss,and etiological characteristics were analyzed. RESULTS Among 126 infants (252 ears),61 were diagnosed with sensorineural hearing loss(48.41%),48 were conductive hearing loss(38.09%),and 17 were found to have normal ABR thresholds(13.49%). The hearing loss was associated with various factors,including history of infection during pregnancy(21 cases),threatened abortion(9 cases),pregnancy with age at or over 35(6 cases),extension of pregnancy(7 cases),history of systematic diseases(10 cases),history of neonatal jaundice(13 cases),history of asphyxia and hypoxia(18 cases),premature and low birth weight neonates(8 cases),neonatal diseases (8 cases),family history of deafness(5 cases),craniofacial deformity(3 cases),central nervous system disorder(6 cases),and 9 cases were second child. CONCLUSION The infants who failed to pass hearing screening have various etiology characteristics in hearing loss. The infants associated with risk factors were mostly found to have sensorineural hearing loss.

OBJECTIVE: To investigate the relationship between the changes of serum neutrophil extracellular traps (NETs), soluble vascular cell adhesion molecule-1(sVCAM-1) and deep venous thromboembolism after knee arthroplasty. METHODS: From May 2017 to April 2020, 30 patients with deep venous thromboembolism after knee arthroplasty were retrospectively selected as the observation group, and 60 patients without deep venous thromboembolism after knee arthroplasty in the same period were randomly selected as the control group. The clinical data, serum levels of nets and sVCAM-1 before and 1, 3 and 5 days after operation were compared between the two groups. Logistic regression model was used to analyze the influencing factors of deep venous thromboembolism after knee arthroplasty; Pearson correlation was used to analyze the relationship between serum nets and sVCAM-1 levels;Draw the receiver operating characteristic curve(ROC) to obtain the area under the curve(AUC), and analyze the diagnostic value of serum nets and sVCAM-1 levels for deep vein thromboembolism after knee arthroplasty. RESULTS: There were statistically significant differences between two groups in age, body mass index, and postoperative knee elevation and flexion ratio(P<0.05). The level of serum NETs and sVCAM-1 on the 1st and 3rd day after surgery of the observation group were higher than the control group(P<0.05). Logistic regression analysis showed that age, body mass index, knee flexion position, serum nets and sVCAM-1 levels at 1 and 3 days after operation were all the influencing factors of DVT after knee arthroplasty (P<0.05);Pearson correlation analysis showed that there was a positive correlation between the levels of serum NETs and sVCAM-1 in patients with deep venous thromboembolism after knee arthroplasty 1 and 3 days after operation(P<0.05). The ROC curve of predicting deep venous thromboembolism after knee arthroplasty by serum nets and sVCAM-1 levels at 1 and 3 days after operation was drawn, the results showed that the AUC of serum nets and sVCAM-1 levels at 1 day after operation was higher than that at 3 days after operation, which had a good predictive effect. CONCLUSION The influencing factors of deep vein thromboembolism after knee arthroplasty are age, body mass index, postoperative knee elevation and flexion, postoperative serum NETs and sVCAM-1 levels, especially postoperative serum NETs and sVCAM-1 levels. Changes can be used as potential biomarkers for predicting postoperative deep vein thromboembolism, and clinical attention should be paid to it.
Humans ; Infant, Newborn ; Arthroplasty, Replacement, Knee/adverse effects* ; Body Mass Index ; Postoperative Complications/etiology* ; Retrospective Studies ; Venous Thromboembolism/etiology*

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology

OBJECTIVETo investigate the expression of protein tyrosine phosphatase non-receptor type 2 (PTPN2) and nuclear factor-kappaB (NF-kappaB), as well as the relationship between their expression and periodontal destruction in mice with diabetic periodontitis.

METHODSFour weeks old healthy C57BL/6J mice were randomly divided into normal control group (Group N), periodontitis group (Group P) and diabetic periodontitis group (Group DP), and each group had six mice. Mice in Group P were inoculated Porphyromonas gingivalis orally to induce periodontitis. Mice in Group DP had high sugary and fatty food, streptozotocin intraperitoneal injection and Porphyromonas gingivalis oral inoculation to induce diabetic periodontitis. All mice were sacrificed 4 weeks after the last bacterium inoculation of Groups P and DP. Stereo microscope was chosen to detect morphological changes and bone loss areas of the alveolar bone. Hematoxylin-eosin (HE) staining was selected to observe loss heights of periodontal attachment. Immunohistochemical staining was used to detect PTPN2 and NF-kappaB expression in periodontal tissues.

RESULTSGroup P and Group DP had significantly more attachment loss heights and areas than Group N (P < 0.05), and showed less PTPN2 expression (P < 0.05) and higher NF-kappaB levels (P < 0.01).

CONCLUSIONPTPN2 may negatively regulate the development of diabetic periodontitis, while NF-kappaB may have opposite effects. PTPN2 down-regulation might contribute to NF-kappaB over-expression leading to exacerbated periodontal destruction.

Objective To observe the expression of PD-L1 in breast cancer tissue and to investigate its correlation with cellu-lar immunity.Methods One hundred and fourteen paraffin-embedded specimens of breast cancer were collected from the Qian′an Municipal People′s Hospital.The expression of PD-L1 in breast tumor tissue was detected by immunohitochemical technique,then the relationship between PD-L1 expression and tumor clinicopathological characteristics was analyzed;the levels of peripheral blood CD3+,CD3+CD4+,CD3+CD8+,CD3-CD19+,CD3-CD16+CD56+cells and CD4+/CD8+in the patients with PD-L1 negative and PD-L1 positive of the two groups were detected by the flow cytometry.Results Among 114 cases of breast cancer specimen,35 ca-ses(30.7%)were PD-L1 expression positive with the expression rate of 30.7%.The PD-L1 expression was correlated with the tumor size,histological grade and Ki-67 high expression(P<0.05);the cellular immunity status in the patients with PD-L1 negative expression was better than that in the patients with PD-L1 positive expression(P<0.05).Conclusion The PD-L1 expression is closely correlated with the poorer clinicopathological characteristics of breast cancer,its mechanism may be correlated with the dis-ruption of cellular immunity in the patients with PD-L1 positive expression.