Objective To investigate the mechanism of IL-1β in promoting glial scar formation after spinal cord injury.Methods The experimental model of SCI was created by extradural compression of the spinal cord using an aneurysm clip.Rats were randomly divided into model group, sham operation group, IL-1β inhibitor IL-1RA group, IL-1β group and IL-1β+JAK2-STAT3 inhibitor AG490 group, according to different interventions, then were given normal saline, IL-1RA, IL-1β and IL-1β+AG490 every 10 μL respectively, sham group received only laminectomy.The motion function of the hindlimbs of rats was measured by Basso Beattie Bresnahan(BBB) scores and the expression of GFAP, vimentin and p-STAT3 were detected by Western blot technique, immunofluorescence assay and immunohistochemistry technique at corresponding time points(at the 8th, 12th hour, 1st, 3rd, 7th and 14th day after SCI).Results The expression trend of p-STAT3(at the 8th and 12th hour after SCI),GFAP and vimentin(at the 7th and 14th day after SCI)was: the expressions of p-STAT3, GFAP and vimentin in the model group were significantly higher compared with the sham group(P<0.01), the expression of p-STAT3,GFAP andvimentin in the IL-1RA group were significantly lower compared with the model group(P<0.05) whereas significantly higher compared with the sham group(P<0.05);the expressions of p-STAT3, GFAP and vimentin in the IL-1β+AG490 group were significantly lower compared with the model group(P<0.05)whereas significantly higher compared with the sham group(P<0.05), the expressions of p-STAT3, GFAP and vimentin in the IL-1β group were significantly higher compared with the model group(P<0.05).Conclusions IL-1β can improve glial scar formation via JAK2-STAT3 signal.Inhibition of IL-1β or JAK2-STAT3 can reduce glial scar formation and promote functional recovery of spinal nerve.

Objective To investigate the protective effects of active components of notoginseng on immunological liver injury in mice. Methods Sixty Kunming mice were randomly divided into normal group (group A), model group (Group B), PNS group (Group C), total flavonoids group (Group D),and polysaccharide group (group E). C,D and E groups were given PNS, total flavonoids and polysaccharide orally, 1/day for 14 days. Then BCG was intravenous injected in B, C, D and E groups, and after 26 days lipopolysaccharide (LPS) was intravenous injected. Samples of eye venous plexus blood were collected, and serum levels of alanine aminotransferase (ALT), total superoxide dismutase (T-SOD) and Interleukin-4 (IL-4) were detected. Organs index was calculated by checking pathological results of liver, spleen and thymus. Results Com-pared with group B, the thymus index and serum ALT levels were significantly decreased in C, D and E groups (P<0.01), but the levels of IL-4 and T-SOD increased significantly (P<0.01). Pathological results showed that there were more serious inflammatory cell infiltration in liver, edema and necrosis of dot in C, D and E groups than those in group B. Conclusion The active components of notoginseng showed a significant protective effect on immunological liver injury.

Objective To investigate whether IL-17 could stimulate the vascular endothelial growth factor (VEGF) production on HaCaT cells alone. We also investigated whether shikonin could inhibited the proinflamation effects of interleukin-17(IL-17) acting on HaCaT cells. MethodsWe examined the expression of VEGF by double antibody sandwich enzyme-linked immunosorbent assay ( ELISA ) and realtime polymerase chain reaction(RT-PCR) in HaCaT cells and the cell supernatant. The viability of HaCaT cells in the drug group was detected by the Cell Counting Kit-8 (CCK-8). ResultsThe expression of VEGF in different time IL-17-stimulated groups on HaCaT cells and the cell supernatant were higher than the control group( P＜0.001 ). The expression of VEGF in different drug treatment groups on HaCaT cells and the cell supematant were lower than the stimulated group by IL-17 ( P＜0. 001 ). The cell viability of different drug treatment groups have no significant difference( P＞0.05 ). ConclusionWe show that IL-17 specifically and time-dependently augmented and induced VEGF expression on HaCaT cells and the cell supernatantThen shikonin markedly inhibited the increase tengency of IL-17 effection on HaCaT cells and the cell supematant level.

AIM: To investigate whether a pathological micro-environmental culture system consisting of cholestatic sera induces embryonic stem cells (ESC) to differentiate into hepatocyte-like cells in vitro, and select hepatic stem cells from differentiating embryonic stem cells. METHODS: Mouse ESC, E14 cell line, were cultured in Dulbecco's modified Eagle's medium containing 106 U/L recombinant mouse leukemia inhibitory factor (rmLIF) and 10% FCS. After embryonic bodies formed by the hanging drop culture method, they were exposed to fibroblast growth factor-4 (FGF-4) and hepatocyte growth factor (HGF) for one week, and then placed to a pathological micro-environmental culture system consisting of 5% cholestatic sera and cultured for 2 weeks. Morphological examination, immunocytochemical staining of albumin and CK8/18 were carried out, and mRNA level of albumin and transthyretin were detected by RT-PCR. Glycogen storage and urea synthesis of the cells were tested with PAS staining and colorimetric assay, respectively. RESULTS: The proliferation of cells was inhibited at the early stage when cultured in a pathological micro-environmental culture system consisting of 5% cholestatic sera, but 2 weeks later, a large number of epithelial-like cell colonies were observed, which exhibited hepatocellular phenotype, expressing albumin and CK8/18, transcribing mRNA of albumin and transthyretin and synthesizing glycogen and urea. CONCLUSION: A pathological micro- environmental culture system consisting of 5% cholestatic sera could not only induce embryonic stem cells to differentiate into hepatocyte-like cells, but select hepatic stem cells from differentiating embryonic stem cells initially induced by FGF-4 and HGF in vitro as well.

Hespintor is an unknown function protein that was got from hepatoblastoma cell lines HepG2 by suppression subtractive hybridization technique (SSH), sequence analysis showed that the protein is a new member of secretory type of Kazal type serine protease inhibitor (Serpin) family, and has high homology with esophageal cancer related gene 2 (ECRG2). The coding sequence of Hespintor's Kazal domain was subcloned into prokaryotic expression vector pET-40b(+), then transformed into Rosetta (DE3). A recombinant protein about 42 kDa in the form of inclusion body was optimization expressed by inducing with 0.25 mmol/L IPTG, 30 degrees C for 5 h. and its specificity was confirmed via Western blotting. The recombinant protein was purified by metal chelate affinity chromatography (MCAC) and anion-exchange chromatography. The preliminary experimental result showed that the recombinant protein can inhibit trysin hydrolysis activity specifically. The result clearly demonstrated that Hespintor, as a novel member of Serpin, would be valuable in developing anti-tumor agents.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; Hep G2 Cells ; Humans ; Proteinase Inhibitory Proteins, Secretory ; Recombinant Proteins ; biosynthesis ; genetics ; Serine Peptidase Inhibitors, Kazal Type ; Serine Proteinase Inhibitors ; biosynthesis ; classification ; genetics

OBJECTIVE: To analyze the changing features of mandarin-tone recognition in lower prelingual children with cochlear implant after mapping. METHOD: Twenty-nine children with CI were registered in this test, who were divided into two groups according to the age received the operation. They were group A whose ages were 3 to 4.5 years old, and group B whose ages were 5.0 to 6.5 years old. The time after first mapping was between 1.5 and -2.0 years. The test only included close-set phonetic recognition which was mainly used to evaluate Mandarin-tone recognition. The Phonetic Recognition List was used as the test material. RESULT: The results showed that the percentages of correct recognition were same-single-syllable tones average (63.00+/-16.75)%; bi-syllable tones average (75. 60+/-11.18)%; single-character words average (72.38+/-11.39)% in A group children and respectively, (49.46+/-13.91)%; (64.71+/-9.64)%; (55.71+/-8.59)% in B group children. The recognition scores exceeded chance level in all results and they were better in A group. Statistical analysis(t test) showed significant difference between two groups. CONCLUSION The age is one of the most influence factors about Mandarin-tone recognition after implanting in pre-lingual children with CI. It is another important factor to influence studying Chinese after operation in the children.
Age Factors ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Deafness ; physiopathology ; Female ; Humans ; Language ; Male ; Speech Discrimination Tests

Objective:To investigate the clinical value of high intensity focused ultrasound (HIFU) ablation combined with levonorgestrel releasing in uterine system (LNG-IUS) in the treatment of adenomyosis.Methods:From January 2015 to January 2018, patients with adenomyosis diagnosed and treated in Obstetrics and Gynecology of our hospital were selected as the research objects. According to the wishes and treatment methods of the patients, the patients were divided into two groups: the combined treatment group was treated with HIFU combined with LNG-IUS, and the HIFU group was only treated with HIFU; the lesion volume and uterine volume reduction rate, hemoglobin, carbohydrate antigen 125 (CA125) and verbal rating scale (VRS) scores were compared between the two groups before and after treatment, and adverse reactions after treatment the scores were recorded.Results:Cases were followed up for 12 months after treatment: the lesion volume reduction rate and uterine volume reduction rate in the combined treatment group were better than those in the HIFU group [(58.8±14.1)% vs (49.3±17.2)%, (37.4±6.2)% vs (32.9±5.0)%, P<0.05]; the hemoglobin level was higher than that in the control group [(113.4±12.8)g/L vs (107.5±10.6)g/L, P<0.05]. In addition, the VRS score of dysmenorrhea in the combined treatment group was also better than that in the HIFU group, with statistically significant difference ( P<0.05). Conclusions:Compared with HIFU ablation alone, patients performed in HIFU combined with LNG-IUS achieved better lesion volume reduction rate and uterine volume reduction rate, and hemoglobin level and dysmenorrhea symptoms improved better in patients with adenomyosis.

Objective To observe the association between the cardiovascular health score and newonset atrial fibrillation.Methods A total of 95 026 participants who participated the health examination between July 2006 and October 2007 at Kailuan group and without history of atrial fibrillation were selected as the observation cohort.The second,the third and the fourth health examination were performed between July 2008 to October 2009,July 2010 to October 2011,July 2012 to October 2013,respectively.A total of 85 028 participants were included in the final analysis after excluding participants who had new-onset valvular atrial fibrillation and participants lost to follow-up.The participants were divided into 4 subgroups by cardiovascular health score at baseline according to the definition of AHA and cardiovascular health scoring system,namely group of 0-6 points (n =11 103),7-8 points (n=24 487),9-10 points (n =32 556),and 11 14 points (n =16 882).The incidence of atrial fibrillation in each subgroup was observed,and the association between cardiovascular health score and risk of new-onset atrial fibrillation was analyzed using multiple Cox regression analysis.Results A total of 254 participants developed atrial fibrillation during the median of (5.6 ± 1.4) years follow-up.The total incidence of new-onset atrial fibrillation was 0.53/1 000 person-year.The incidence of atrial fibrillation was 0.69/1 000 person-year,0.60/1 000 person-year,0.56/1 000 person-year,and 0.30/1 000 person-year,respectively in 0-6 points,7-8 points,9-10 points,and 11-14 points subgroups,respectively (P ＜ 0.01).After adjustment of age,gender,education level,income,drink,history of myocardial infarction,history of stroke,serum uric acid and C reactive protein level,multiple Cox regression analysis showed that one health score point increase was related to 8％ reduction of new onset atrial fibrillation(HR =0.92,95％ CI 0.86-0.99,P ＜ 0.05).Compared with the group of 0-6 points group,the risk of atrial fibrillation in the group of 11-14 points group was reduced by 49％ (HR =0.51,95 ％ CI 0.31-0.83,P ＜ 0.01).Conclusion The risk of new-onset atrial fibrillation is reduced in proportion to increase of cardiovascular health score.

Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.

The prognosis for diffusely infiltrating gliomas at World Health Organization (WHO) grade 2-4 remains dismal due to their heterogeneity. The rapid development of genome-wide molecular-profiling-associated studies has greatly promoted the accuracy of glioma classification. Thus, the latest version of the WHO classification of the central nervous system tumors published in 2021 has incorporated more molecular biomarkers together with histological features for the diagnosis of gliomas. Advanced usage of molecular pathology in clinical diagnostic practice provides also new opportunities for the therapy of patients with glioma, including surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy, and more precision clinical trials. Herein, we highlight the updates in the classification of gliomas according to the latest WHO guidelines and summarize the clinically relevant molecular markers by focusing on their applications in clinical practice. We also review the advances in molecular features of gliomas, which can facilitate the development of glioma therapies, thereby discussing the challenges and future directions of molecular pathology toward precision medicine for patients with glioma.