Objective:To investigate the value of biopsies on diagnosing cervical intraepithelial neoplasia of grade 2 or worse (CIN Ⅱ +), and optimize biopsy procedures of risk-based colposcopy practice. Methods:A prospective study was performed on 346 women referred to colposcopy following abnormal cervical cancer screening results at the First Affiliated Hospital of Nanjing Medical University, from April 2017 to December 2019. Up to 4 cervical biopsies were taken during colposcopy and each biopsy specimen was evaluated separately in histology. CIN Ⅱ + identified by any biopsy was the reference standard of disease used to evaluate the diagnostic value of targeted biopsy and random biopsy, and to quantify the improved detection of CIN Ⅱ + by taking multiple biopsies. Cervical cytology, HPV genotyping, and colposcopic impression were used to establish different risk strata to select various multiple biopsies procedures during colposcopy to improve accuracy and efficiency of CIN Ⅱ + detection. Results:In total 346 women, 190 (54.9%, 190/346) cases of them were diagnosed as CIN Ⅱ +. (1) In total 346 women, 96.8% (184/190) CIN Ⅱ + were detected by targeted biopsies, 27.9% (53/190) CIN Ⅱ + were detected in biopsies targeted grade 1 abnormal colposcopic findings (G1) on the cervix, and 68.9% (131/190) CIN Ⅱ + were detected in biopsies targetrd grade 2 abnormal colposcopic findings (G2) on the cervix. Colposcopy had a sensitivity of 68.9% when the biopsy threshold was G2, sensitivity increased to 96.8% when the biopsy threshold was defined to be G1. Among women with G1, adding 2 targeted biopsies to the first biopsy were sufficient to detect all CIN Ⅱ +, among women with G2, adding 1 targeted biopsy was sufficient. (2) Among 270 women, random biopsies targeted normal colposcopic findings on the cervix were performed in addition to targeted biopsies and in total 3.2% (6/190) additional CIN Ⅱ + were detected. As the number of cervical quadrants involved by abnormal colposcopic images increased, random biopsy detected fewer CIN Ⅱ + that would have otherwise been missed by targeted biopsies ( P=0.010). (3) Women with atypical squamous cells,cannot exclude high grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL) or atypical glandular cell (AGC) referral cytology, HPV 16-positive, G2 were more likely to have CIN Ⅱ +( P<0.01); for those meeting only one category, the yield of CIN Ⅱ + increased from 34.0% for one biopsy to 51.0% for two biopsies, the absolute increase in CIN Ⅱ + yield increased from the first to the second biopsy was 17.0%, two biopsies were sufficient to detect all CIN Ⅱ +; for those meeting at least two categories, the yield of CIN Ⅱ + increased from 90.7% for one biopsy to 92.6% for two biopsies, the absolute increase in CIN Ⅱ + yield increased from the first to the second biopsy was 1.9%, two biopsies were sufficient to detect all CIN Ⅱ +; for those not meeting any category, the yield of CIN Ⅱ + increased from 8.8% for one biopsy to 17.6% for two biopsies, to 23.5% for three biopsies, the absolute increase in CIN Ⅱ + yield increased from the first to the second biopsy, from the second to the third biopsy was 8.8%, 5.9%, three biopsies were sufficient to detect all CIN Ⅱ +. Conclusions:Performing multiple targeted biopsies could improve efficiency of CIN Ⅱ + detection. Adding random biopsies to multiple targeted biopsies showed very limited additional benefit for detection of CIN Ⅱ +. The biopsy procedures undertaken during the colposcopy visit could be modified based on various colposcopic impressions and reasons for referral.

OBJECTIVE: To determine the levels of visfatin in patients with chronic kidney disease (CKD) and to explore the relationship between visfatin levels and caroid atherosclerosis in CKD patients. METHODS: A total of 180 CKD patients (102 non-dialyzed patients and 78 dialysis patients) and 42 healthy subjects enrolled in this study. The serum levels of visfatin, IL-6, and high sensitive C-reactive protein (hsCRP) were measured by ELISA. Common carotid arteries intima-media thickness (CCA-IMT), cross-sectional calculated intima-media thickness (c IMT) area and atherosclerotic plaque were detected by non-invasive high-resolution B-mode ultrasonography. RESULTS: The serum levels of visfatin, IL-6 and hsCRP were significantly increased in CKD patients compared with age matched healthy subjects (P<0.01). The serum levels of visfatin, IL-6 and hsCRP in the dialyzed patients were significantly higher than those in non-dialyzed patients (P<0.05). Visfatin levels increased with the progression of renal dysfunction and inversely related to creatinine clearance (Ccr) in non-dialyzed patients (r=-0.415, P<0.05). Patients with carotid artery plaques showed significantly higher levels of visfatin[(34.22±7.96) ng/mL)] compared with those without plaques [(28.24±6.18) ng/mL, P<0.05]. The serum levels of visfatin were closely correlated with IL-6 (r=0.548, P<0.001), hsCRP (r=0.430, P<0.001), CCA-IMT (r=0.462, P<0.05), and c IMT area (r=0.411, P<0.05). After adjusting for GFR, age, gender, and other risk factors associated with atherosclerosis, multiple stepwise regression analysis showed that serum visfatin is a independent risk factor for CCA-IMT (β=0.433, P<0.01) and c IMT area (β=0.412, P<0.01). CONCLUSION The serum level of visfatin increase with the progression of CKD and should be considered to be a new risk factor for atherosclerosis in CKD.
Adult ; Aged ; C-Reactive Protein ; metabolism ; Carotid Artery Diseases ; blood ; complications ; Case-Control Studies ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; blood ; Renal Insufficiency, Chronic ; blood ; complications ; Risk Factors

Objective:To prepare and characterize cyclodextrin inclusion complexes of regorafenib and to investigated their antitumor effects.Methods:Three inclusion complexes (RG-β-CD,RG-γ-CD,RG-Hp-β-CD) were prepared by recrystallization and solvent evaporation methods between regorafenib (RG) and β-cyclodextrin (β-CD),γ-cyclodextrin (γ-CD) and hydroxypropyl-β-cyclodextrin (Hp-β-CD),respectively.The compounds were characterized by Fourier transform infrared spectroscopy (FT-IR),thermogravimetric analysis (TG),differential scanning calorimetry (DSC),powder X-ray diffraction (PXRD),1 H nuclear magnetic resonance (1H-NMR),nuclear overhauser effect spectroscopy (NOESY).Human colon cancer SW620 cells were inoculated to Balb/c-nu nude mice,PBS,RG or RG-β-CD were given orally for 3 weeks,and the volumes of tumor were determined and compared among 3 groups.Results:The solubility and dissolution were improved after inclusion with 3 kinds of cyclodextrins.RG-β-CD had the best stability,followed by RG-γ-CD inclusion.The in vivo study showed that the tumor suppressive effect of RG-β-CD was stronger than that of regorafenib.Conclusion:The bioavailability of regorafenib by inclusion with cyclodextrin is enhanced due to the increased solubility,which can provide an effective method for improving solubility and dissolution of antitumor agents.

Bone marrow-derived mesenchymal stem cells (BMSCs) for repairing damaged heart tissue are a new kind of important treatment options because of their potential to differentiate into cardiomyocytes. We in this experiment investigated the effect of different electrical stimulation time on the expression of myocardial specificity gene and protein in rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The rBMSCs of second or third generation were randomly divided into three groups, i.e, electrical stimulation (ES) group, 5-Azacytidine (5-Aza) group and the control group. The rBMSCs in the ES groups with complete medium were exposed to 2 V, 2 Hz, 5 ms electrical stimulation for 0. 5 h, 2 h, 4 h, and 6 h respectively every day for 10 days. Those in the 5-Aza group were induced by 5-Aza (10 μmol/L) for 24 h, and then cultured with complete medium for 10 days. Those in the control group were only cultured with complete medium, without any treatment, for 10 days. The rBMSCs' morphological feature in each group was observed with inverted phase microscope. The mRNA expression of myocyte-specific enhancer factor 2C (MEF-2C) and connexin 43 (Cx43) were examined with Real-Time quantitative PCR and the protein expression of MEF-2C, Cx43 were detected with Western Blot method. The results showed that the mRNA expression level of the MEF-2C, Cx43 and the protein expression level of MEF-2C, Cx43 were significantly higher in the ES group and 5-Aza group than those in the relative control group (P < 0.05). It suggests that electrical stimulation could play a part of role in the induction of the rBMSCs to differentiate into the cariomyocyte-like cells in vitro and the effectiveness of the electrical stimulation with 2 h/d had the best in our experiment. But the mechanism how electrical stimulation promotes the differentiation of rBMSC into cardiomyocyte is still unclear.
Animals ; Biomarkers ; metabolism ; Cell Differentiation ; Cells, Cultured ; Connexin 43 ; metabolism ; Electric Stimulation ; MEF2 Transcription Factors ; metabolism ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Myocytes, Cardiac ; cytology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the clinical efficacy and prognosis of transjugular intrahepatic portosystemic shunt (TIPS) and drug combined with endoscopic treatment in patients with liver cirrhosis and esophagogastric variceal bleeding (EGVB).Methods:From January 2012 to December 2013, at the First Affiliated Hospital of Xi′an Jiaotong University, the data of 147 patients with liver cirrhosis and EGVB undergoing TIPS or drug combined with endoscopic treatment were retrospectively collected, with 87 cases in TIPS treatment group and 60 in drug combined with endoscopic treatment group.The 5 years follow-up data were analyzed, and the overall survival rates, rebleeding-free survival rates and hepatic encephalopathy-free survival rates at 6 weeks, 1 year, 2 years and 5 years after treatment of two groups were compared. Independent sample t test, Mann-Whitney U test, chi-square test, Fisher exact test, Z test, log-rank test and trend test were used for statistical analysis. Results:There were no significant differences in age, gender, etiology, Child-Pugh classification, initial liver function, coagulation function, liver ascites, previous history of hepatic encephalopathy, blood pressure and preoperative blood transfusion history between the TIPS treatment group and combination of drugs and endoscopy treatment group (all P>0.05). Forty-one patients died within 5 years, of which 20 (48.8%) died of rebleeding and 6 (14.6%) died of hepatic encephalopathy. There were no significant differences in 6-week, 1-year and 2-year overall survival rates between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year overall survival rate of the TIPS treatment group was higher than that of the drug combined with endoscopic treatment group (78.4% vs. 63.2%), and the difference was statistically significant ( Z=2.06, P=0.048). The 6-week, 1-year, 2-year, 5-year rebleeding-free survival rates of the TIPS group were 97.7%, 96.5%, 88.9% and 70.9%, respectively, which were all higher than those of the drug combined with endoscopic treatment group (86.7%, 53.3%, 43.3% and 27.1%), and the differences were statistically significant ( Z=2.35, 6.39, 6.26 and 4.80, all P<0.05). There were no significant differences in hepatic encephalopathy-free survival rates at 6 weeks, 1 year and 2 years after treatment between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year hepatic encephalopathy-free survival rate of the TIPS treatment group was lower than that of the drug combined with endoscopic treatment group (67.7% vs. 86.7%), and the difference was statistically significant ( Z=2.28, P=0.030). The lower the Child-Pugh classification, the higher the cumulative 5-year survival rate ( χ2=6.75, P<0.01). There was no statistically significant difference in the 5-year overall survival rate in patients with the same Child-Pugh classification between the TIPS group and the drug combined with endoscopic treatment group (all P>0.05). Conclusions:The efficacy of TIPS is better than that of the drug combined with endoscopic treatment in treating EGVB. Even the long-term risk of hepatic encephalopathy of TIPS is higher, the short-term, middle-term and long-term rebleeding rate are decreased. Patients with Child-Pugh grade C do not need to avoid TIPS when choosing the treatment, the earlier the TIPS used, the better survival benefit will be obtained.

Objective:To investigate the predictive value of the monocyte-to-lymphocyte ratio (MLR) for survival in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:92 cases with HBV-ACLF who were admitted to the General Hospital of Western Theater Command from October 2014 to October 2017 were selected. Clinical indicators were retrospectively collected, and their survival condition was followed up for 90 days, with the end point as death or liver transplantation. MLR levels predictive value among patients after 90 days of involvement was compared by analyzing the differences between the survival and death groups and its correlation with various indicators of liver function for prognosis.Results:92 cases were included in this study, with a 90-day survival rate of 52% (48/92), and a mortality rate of 48% (44/92). MLR for survival and death groups were 0.520 (0.310, 0.828) and 0.740 (0.440, 1.120), respectively. MLR level was significantly higher in the death than survival group ( P<0.05). Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) and 95% confidence interval for the survival group was 0.640 (0.527-0.754). The cutoff value for MLR was 0.399 at which the sensitivity and specificity were 0.864 and 0.396, respectively. Survival analysis showed that the 90-day survival rate was significantly lower in the high MLR group than corresponding low MLR group ( P=0.011). Logistic multivariate regression analysis showed that after adjusting for other factors, MLR level was an independent prognostic factor in patients with HBV-ACLF. Conclusions:MLR can be used as a potential prognostic indicator for patients with HBV-ACLF, and its clinical value needs to be verified by large-scale prospective randomized trials.

Objective To analyze the performance of colposcopy and investigate the diagnosis and treatment characteristics of high-grade squamous intraepithelial lesion (HSIL) diagnosed by cervical tissue sampling in post-menopausal women. Methods A retrospective study was performed on 1 449 patients with HSIL diagnosed by cervical tissue sampling under colposcopy and treated by loop electrosurgical excision procedure (LEEP) or extrafascial hysterectomy as the primary therapy at the First Affiliated Hospital of Nanjing Medical University, from November 2015 to October 2017. In order to investigate the diagnosis and treatment of HSIL in post-menopausal women, a case-control study was conducted to compare the difference in performance of colposcopy and treatment modality between 213 post-menopausal patients (14.7%, 213/1 449) and 1 236 pre-menopausal patients (85.3%, 1 236/1 449). Results (1)The proportion of cases pathologically upgraded to cervical cancer was significantly greater in post-menopausal patients (9.4%, 20/213) compared with pre-menopausal patients (3.8%, 47/1 236; P<0.05). (2) The proportion of ≥HSIL diagnosed by colposcopy showed no significant difference between post-menopausal patients (76.1%, 162/213) and pre-menopausal patients (78.2%, 967/1 236; P=0.479). The proportion of typeⅢtransformation zone (TZ) was significantly greater in post-menopausal patients (91.1%, 194/213) compared with pre-menopausal patients (59.1%, 731/1 236; P<0.05). The rate of missed diagnosis of cervical cancer was significantly higher in typeⅢTZ (6.4%, 59/925) compared with typeⅠand(or)ⅡTZ (1.5%, 8/524; P<0.05). The proportion of HSIL detected by endocervical curettage alone was greater in post-menopausal patients (9.9%, 21/213) compared with pre-menopausal patients (2.6%, 32/1 236; P<0.05). (3)Initial treatment with LEEP: the positive rate of endocervical margin was significantly greater in post-menopausal patients (20.5%, 36/176) compared with pre-menopausal patients (10.5%, 130/1 236;P<0.05); in patients who were diagnosed as HSIL after LEEP, the positive rate of endocervical margin and the residual rate were both greater in post-menopausal patients compared with pre-menopausal patients [15.4% (25/162) versus 8.8% (105/1 189), P=0.008; 52.0% (13/25) versus 26.7% (28/105), P=0.014]. (4)Thirty-seven post-menopausal patients were treated by extrafascial hysterectomy as the primary therapy, 5 cases (13.5%, 5/37) were diagnosed as cervical cancer (stage Ⅰa1) after the surgery. Conclusions (1) The lesions of HSIL in post-menopausal patients still have definite features under colposcopy as same as pre-menopausal patients. Endocervical curettage could help detect more HSIL in post-menopausal patients. Compared with pre-menopausal patients, post-menopausal HSIL patients have an increased risk of cervical cancer and are more likely missed by cervical tissue sampling. (2) LEEP has the dual effects of diagnosis and treatment, and is still the recommended treatment for post-menopausal HSIL patients. However, the increase in positive rate of endocervical margin and residual rate requires further active intervention. (3) Considering those post-menopausal HSIL patients who cannot accept conization as the initial treatment, the selection of hysterectomy type requires more thorough study.

With the rapid development of neuroimaging technology and related data processing methods, multimodal neuroimaging has been widely used in research fields such as neuroscience and clinical diseases. In this paper, the current development of multimodal neuroimaging fusion algorithm and its application in the diagnosis and treatment of brain diseases were reviewed. The definitions, applications, and advantages of the three levels of multimodal neuroimaging fusion, i.e. early fusion, late fusion, and intermediate fusion, were introduced and analyzed. The commonly used multi-modal neuroimaging algorithm basing on signal source separation method and deep multi-modal learning was introduced. The application of multimodal neuroimaging technology in the diagnosis and treatment of severe brain diseases such as schizophrenia and Alzheimer's disease was further discussed. Finally, the existing challenges and future research directions of multimodal neuroimaging methods and applications were summarized.

Objective:To investigate the prognosis-related factors and its predictive value in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:Sixty-three cases with HBV-ACLF were enrolled. According to the prognosis of 4-weeks, patients were divided into survival and death group. Univariate and multivariate analyses were performed on the clinical data of the two groups of patients to screen the risk factors affecting prognosis, evaluate its predictive value, and compare them with the MELD score, CTP score, and CLIFACLF score. The data were analyzed using t-test, Mann-Whitney U test, χ2 test. Multiple logistic regression analysis was used for multiple risk factors. Results:There were 63 cases with HBV-ACLF, with 16 cases (25.40%) in the 4-week survival group, and 47 cases (74.60%) in the death group. The survival group age was 38.38 ± 14.50 years, which was significantly lower than the age of the death group 52.28 ± 12.51 years ( P < 0.001). The survival group alpha-fetoprotein (AFP) level was 91.21 (8.38 ~ 154.10)μg/L, which was significantly higher than the level of the death group [12.60 (5.70 ~ 33.80) μg/L, P = 0.039]. The survival group alanine aminotransferase (ALT) level was 925.65 (523.43 ~ 1 364.80) U/L, which was much higher than that of the death group [371.60 (117.30 ~ 895.30) U/L, P = 0.040]. The survival group serum sodium level was (136.59 ± 4.03) mmol /L, which was significantly higher than the level of the death group [(132.22 ± 6.37) mmol/L, P = 0.013]. The survival group ascites severity level was much lower than that of the death group ( P = 0.008). The survival group creatinine level was 56.50(49.43 ~ 86.25) μmol/L, which was much lower than the level of the death group [86.20 (68.00 ~ 143.00) μmol/L, P = 0.003]. Multivariate logistic regression analysis showed that ascites ( OR = 0.470, 95% CI: 0.226 ~ 0.977) and age ( OR = 0.941, 95% CI: 0.888 ~ 0.996) were risk factors affecting the HBV-ACLF prognosis. The area under the curve predicted liver failure prognostic score for ascites and age was 0.821, and the sensitivity and specificity were 68.8% and 87.2%, which was higher than the area under the curve predicted by the MELD score, CTP score, and CLIFACLF score, respectively. Conclusion:Age and ascites can be used to predict the clinical outcome in patients with HBV-ACLF. Younger patients without ascites have a higher survival rate at 4-weeks, but older patients with ascites are more likely to have a lower survival rate.

In order to improve the drug's solubility, dissolution and bioavailability, RG-β-CD, RG-γ-CD and RG-Hp-β-CD were prepared by co-crystallization between Regorafenib (RG) and β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-β-cyclodextrin (Hp-β-CD).Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD),H nuclear magnetic resonance (H-NMR), nuclear overhauser effect spectroscopy (NOESY).experiments, tumor suppression assay were made with SW620 colon cancer cell.The ability of solubility and dissolution were improved after inclusion with three kinds of cyclodextrins. The regorafenib-β-cyclodextrin inclusionis proved to have the best stability. The less enhanced was regorafenib-γ-cycl-odextrin inclusion. The best dissolution of regorafenib-β-cyclodextrin inclusion complex was to bring as the tumor suppression assay, the result shows that regorafenib inclusion with β-cyclodextrin is better than regorafenib itself.The bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to the solubility enhancement of RG, which can provide an effective method for improving solubility and dissolution of insoluble drug in clinical medication.