ObjectiveTo explore the role of saikosaponin D （SSD） targeting signal transducer and activator of transcription 3 （STAT3） in inducing apoptosis of bladder cancer cells by computer-aided drug design and experimental verification. MethodThe druggability and biotoxicity of SSD were explored by Bayesian classifier modeling. The information about SSD， the active ingredient of Bupleuri Radix， was searched against the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform （TCMSP）. The targets of SSD were predicted by PubChem， TCMSP， a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）， Coremine， an Encyclopedia of Traditional Chinese Medicine （ETCM）， and SwissTargetPrediction. GeneCards， Therapeutic Target Database （TTD）， and Online Mendelian Inheritance in Man （OMIM） were employed to predict the potential therapeutic targets of bladder cancer. Then， the common targets shared by SSD and bladder cancer were selected for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Molecular docking was adopted to explore the binding affinity and structural stability of SSD with target proteins. Cytoscape 3.9.1 was used to construct the STAT3-drug regulatory network and STAT3-apoptosis regulatory network. UM-UC-3 cells were treated with 0， 5， 10， 15 μmol·L^-1 SSD for 24 h. Then， flow cytometry was used to detect the apoptosis of bladder cancer cells， and Western blot was employed to determine the protein levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， STAT3， and phosphorylation （p）-STAT3. ResultBayesian classifier modeling and molecular docking showed that SSD had low biotoxicity and bound well to the target protein STAT3 to form a stable protein-ligand complex. There were 282 common targets between bladder cancer and SSD， among which STAT3 was the most central target. The GO enrichment analysis showed that the potential core therapeutic targets involved 3 036 biological processes， 82 cellular components， and 171 molecular functions. The KEGG enrichment analysis showed that the potential core targets were mainly related to the C-type lectin receptor signaling pathway， Toll-like receptor signaling pathway， and cell apoptosis pathway. The STAT3-drug regulatory network and STAT3-apoptosis regulatory network showed that 29 drugs interacted with STAT3， and 27 apoptosis-related genes had a strong correlation with STAT3. Flow cytometry showed that the apoptosis rate increased with the increase in SSD concentration （P<0.05）. Western blotting results showed that SSD down-regulated the protein levels of p-STAT3 and Bcl-2 and up-regulated the protein levels of Bax and Bad in a concentration-dependent manner （P<0.05）. ConclusionSSD has good druggability and low biotoxicity. It may promote the apoptosis of bladder cancer cells by targeting STAT3.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:To explore the role of 17β-estradiol(17β-E2) derived from the hippocampus and gonad in the cognitive memory during the reconsolidation period of fear memory in rats with post-traumatic stress disorder(PTSD).Methods:The 8-week-old clean grade female SD rats were used for this study. Single prolonged stress combined with context fear conditioning was used to prepare the rat PTSD model.(1) Gonad estradiol experiment: 50 female rats were randomly divided into blank control group, model group, sham ovariectomy group, ovariectomy group, and ovariectomy+ estradiol group by random number table method, with 10 rats in each group. The rats in model group, sham ovariectomy group, ovariectomy group, and ovariectomy+ estradiol group were established PTSD model. Rats in ovariectomy group and ovariectomy+ estradiol group underwent ovariectomy, while rats in sham ovariectomy group only were removed adipose tissue of the same mass around the ovaries. And the rats in ovariectomy+ estradiol group were injected with 17β-E2(1 mg/kg, once a day for 14 days) 7 days after ovariectomy.(2) Hippocampal estradiol experiment: 40 female rats were randomly divided into blank control group, model group, hippocampal solvent control group and hippocampal estradiol inhibitor group by random number table method, with 10 rats in each group.The rats in model group, hippocampal solvent control group and hippocampal estradiol inhibitor group were established PTSD model.Rats in hippocampal estradiol inhibitor group were given letrozole once(bilateral, 0.5 μL per side) during the fear memory consolidation period) and rats in the hippocampus solvent control group were injected once with dimethyl sulfoxide in the hippocampus(bilateral, 0.5 μL per side) . The open field test and elevated cross maze test were used to evaluate the anxiety level and autonomous exploration ability, the freeze test was used to evaluate the fear memory, the new object recognition test was used to evaluate the non-spatial memory, and ELISA was used to detect serum 17β-E2 level. SPSS 25.0 software was used for data analysis, and one-way ANOVA was used for inter group comparisons, LSD test was used for further pairwise comparisons.Results:(1)In the gonad estradiol experiment, there were statistical differences in various indicators among the five groups of rats in the open field test, elevated cross maze test, freeze test, and new object recognition test( F=20.200, 12.702, 7.514, 10.094, 7.899, 13.211, all P<0.05). The number of upright times, central area activity time, distance and frequency of entering the open arm, and cognitive index of the model group rats were all lower than those of the blank control group(all P<0.05), and the freezing time was higher than that of the blank control group( P<0.05). The number of upright positions((11.20±1.55) times), central area activity time((11.33±1.80) s), distance((1.49±0.26) m) and times((10.00±1.50) times) entering the open arm, the freezing time((92.20±6.07) s) and cognitive index((60.40±3.71)%) in ovariectomy+ estradiol group were all higher than those of ovariectomy group((4.90±0.65) times, (4.31±1.07) s, (0.49±0.06) m, (3.10±0.62) times, (60.30±5.28) s, (32.60±8.08)%)(all P<0.05). (2) In the hippocampal estradiol experiment, there were statistical differences in various indicators among the four groups in the open field test, elevated cross maze test, freeze test, and new object recognition test( F=40.831, 5.553, 9.087, 5.848, 7.657, 9.191, all P<0.05). The numbers of upright positions, distance and frequency of entering open arms of the model group rats were lower than those of the blank control group(all P<0.05). The number of upright positions((3.00 ± 0.39) times), distance of entering open arm((1.17±0.37) m), freezing time((46.70±3.57)s), and cognition index((29.60±2.70)%) in the hippocampal estradiol inhibitor group were all lower than those in the hippocampal solvent control group((10.10±1.40) times, (4.02±0.79) m, (93.70±9.73) s, (54.20±5.08)%)(all P<0.05). Conclusion:17β-E2 derived from the hippocampus and gonad both had ameliorative effect on cognitive memory and anxiety-like behavior in the reconsolidation period of fear memory in PTSD model rats.

【Objective】 To understand the situation of free blood use of blood donors in Changsha to explore the correlation between free blood use of donors and repeated blood donation behaviors, so as to provide a theoretical basis for the recruitment of voluntary blood donations. 【Methods】 A total of 260 voluntary blood donors were selected by random sampling and divided into reimbursed group(n=97) and unreimbursed group(n=163), based on the results of a questionnaire, inquiring their using of free blood. 【Results】 The reimbursed group differed from the unreimbursed group in all dimensions, including behavioral attitude dimension(Z=3.250, P<0.05), subjective behavioral norm dimension(Z=4.576, P<0.05), and perceptual behavioral control dimension(Z=7.255, P<0.05) and the total score of the scale(Z=8.625, P<0.05), and the differences were statistically significant. 【Conclusion】 The intention to donate again was stronger in donors who experienced free blood use than those didn’t. Such donors are suitable candidates for blood donor recruitment. It is recommended to develop a suitable recruitment strategy for this population and further guarantee the clinical use of blood.

ObjectiveTo investigate the risk factors for portal vein thrombosis (PVT) in cirrhotic patients with esophageal varices, and to establish a nomogram for predicting the risk of PVT. MethodsA retrospective analysis was performed for the clinical data of 283 cirrhotic patients with esophageal varices who attended Shandong Provincial Hospital Affiliated to Shandong University from December 2013 to December 2018, and according to imaging findings, the patients were divided into PVT group with 119 patients and non-PVT group with 164 patients. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to screen out independent risk factors; a nomogram was established and validated based on the results of the multivariate logistic regression analysis, and C-index and calibration curve were used to evaluate its performance. ResultsThe univariate analysis showed that compared with the non-PVT group, the PVT group had significantly higher Child-Pugh class (χ2=9.388, P=0.009), proportion of patients with a history of splenectomy (χ2=26.805, P＜0.001), white blood cell count (Z=-2.248, P=0.025), platelet count (Z=-3.323, P=0.001), D-dimer(Z=-6.236, P＜0.001), and spleen thickness (Z=-2.432, P=0.015) and a significantly lower level of triglyceride (TG) (Z=-4.150, P＜0.001). The multivariate logistic regression analysis showed that a reduction in TG (odds ratio ［OR］=0.441, 95% confidence interval ［CI］: 0.190-0.889), an increase in D-dimer (OR=1.151, 95%CI: 1.041-1.272), prolonged prothrombin time (PT) (OR=1160, 95%CI: 1.025-1.313), and a history of splenectomy (OR=2.933, 95%CI: 1.164-7.389) were independent risk factors for PVT in cirrhotic patients with esophageal varices. In addition, a nomogram was established based on the results of the multivariate regression analysis, with a C-index of 0.745, and the calibration curve showed good consistency between the observed and predicted values for the development of PVT. ConclusionA reduction in TG, an increase in D-dimer, prolonged PT, and a history of splenectomy are independent risk factors for PVT in cirrhotic patients with esophageal varices, and the nomogram developed based on these results can provide a quantitative and intuitive tool for clinicians to assess the risk of PVT.

Objective To investigate the auxiliary effect of artificial tiger bone powder on the fragile fracture healing and functional recovery.Methods From June 2014 to June 2015,64 patients with fragile fracture in the second Hospital of Tangshan were randomly divided into treatment and control groups,32 cases in each group.All the selected patients were given routine treatment of fracture.The treatment group was given artificial tiger bone powder,while the control group was given vitamin D and calcium carbonate.The clinical fracture healing time of the selected patients were recorded.At the beginning and 3,6 months after treatment,the Barthel Index ( BI) and functional independent measure ( FIM) were recorded.Results There was no significant difference in general condition, BI score and FIM score between the two groups before treatment.At the 3rd and 6th month after treatment,the BI scores were(( 65.74 ± 7.94 ),( 76.05 ±8.07 ) value),and FIM scores were(( 76.61± 9.08),(( 87.91 ± 6.76) valu)],those in the treatment group were higher than those in the control group( BI:( 61.12 ± 8.67), ( 71.25 ± 8.32) value and FIM:(71.03±9.34),(79.01±7.32) value),( P＜0.05).The the fracture healing time in the treatment group was shorter((12.78±2.09) weeks) than that in the control group((13.94± 2.32) weeks),( t＝2.101,P＜0.05).Conclusion Artificial tiger bone powder can shorten the healing time of fracture, which has auxiliary effect on the healing of fragile fracture.It can promote the functional recovery of fragile fracture patients,and improve their life and activity.

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

Objective To investigate the effect of ultrasound-guided paravertebral nerve block on stress reaction in patients undergoing esophageal resection. Methods Eighty patients scheduled to do the operation of esophageal resection were randomly divided into two groups with 40 cases in each group. The patients in group A were given the general anesthesia combined with ultrasound-guided paravertebral block, and the patients in group B were given the general anesthesia only. Both of two groups received postoperative patient controlled intravenous analgesia (PCIA). The amount of propofol and remifen-tanil used were recorded. The data of blood pressure, heart rate (HR) and pulseoxygen saturation (SpO2) before anesthesia (T1), before induction (T2), after intubation (T3), in 2 h of surgery (T4), after surgery (T5), 1 h after surgery (T6), 8 h after surgery (T7), 24 h after surgery (T8), 48 h after surgery (T9)were recorded. The analgesic effect was measured by VAS scores and Ramsay sedation scores were also recorded at T6-T10. The levels of blood glucose, epinephrine (E), norcpincphrinc (NE) and dopamine (DA) were also detected at T1, T4, T5, T9. Results The amount of propofol and remifentanil used in group A were lower than those in group B: (960.0 ± 216.9) mg vs. (1 242.5 ± 200.2) mg, (1.5 ± 0.4) mg vs. (2.3 ± 0.4) mg, P<0.05. The patients in two groups successfully completed surgery, and intraoperative vital signs was stable. The quiet and active VAS scores at T6-T9 in group A were significantly lower than those in group B (P<0.05). The Ramsay sedation scores at each time point in two groups had no significant differences (P>0.05). The levels of blood glucose and NE at T9 were significantly higher than those at T1, T4 or T5 of same group, P<0.05.The level of E at T4 and T5 was significantly lower than that at T1 and T9 of same group, P<0.05. The level of DA at T9 was significantly higher than that at T1, T4 and T5 in group B (P<0.05). The levels of blood glucose, NE, E and DA at T9 in group B were significantly higher than those in group A (P<0.05). Conclusions General anesthesia combined with ultrasound-guided paravertebral nerve block could offer favorable anaesthesia effect. It could decrease stress reaction and anesthetics requirements in patients undergoing esophageal resection.

Objective Summarize the experiences of treating after-operation ventricular electrical storm (VES) with extra-corporeal membrane oxygenation (ECMO) .Methods Examine the clinical data of seven cases of treating after-operation VES with ECMO from January 2013 to April 2014 and analyze the basic pre-operation conditions of the patients ,diagnoses ,causes of VES ,ai-ding processes with ECMO ,and prognoses .Results Seven patients all were successfully separated from the machine after the treat -ment ,one patient infected seriously after being separated from the machine ,having multiple organ failure one week later and dis-charged voluntarily ;one patient having cerebral hemorrhage two days later after being separated from the machine and discharged voluntarily ;the remaining five patients cured and discharged with no complications .Conclusion ECMO can provide effective circu-lar support to patients suffering VES after heart operation ,maintaining coronary blood supply ,avoiding further myocardial damage , stabilizing electrolytes and the internal environment ,and gain time for restoration of heart rhythm and treatment according to the causes and triggers .

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.