The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.

Objective To investigate the technical and therapeutic effects of laparoscopic surgery for adult patients with Dong Type C bile duct dilatation.Methods A retrospective cohort study approach was used.The clinical data of 47 patients with Dong Type C adult biliary dilatation who underwent surgery in Fujian Provincial Hospital from January 2014 to December 2017 were collected.There were 12 males and 35 females.The age ranged from 16 to 68 years,with a median age of 30 years.According to different surgical methods,the patients were divided into the laparoscopic group (treated with laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy,n =21) and the open group (treated with traditional open operation,n =26).The intraoperative blood loss,complication rate,operation time,postoperative intestinal function recovery time and postoperative hospital stay were observed.Measurement data with normal distribution were expressed as mean ± standard deviation (Mean ±SD) and analyzed by t test.Comparison of count data was done by the chi-square test.Results There was no perioperative deaths in either group.There was no significant difference in intraoperative blood loss and complication rate between the two groups (P ＞ 0.05).The operation time of the laparoscopic group was significantly longer than that of the open group[(333.7 ±61.1) min vs (235.9 ±64.3) min],with statistically significant difference between graps (P =0.000).The recovery time for the intestinal function of the laparoscopic group was significantly shorter than that of the open group [(2.2 ± 0.5) d vs (2.9 ± 0.6) d],with statistically significant difference between groups (P =0.000).The postoperative hospital stay in the laparoscopic group was significantly shorter than the open group [(7.1 ± 1.8) d vs (12.0 ± 5.9) d],with statistically significant difference between groups (P =0.001).Conclusion For adult biliary dilatation patiens with Dong Type C,laparoscopic surgery is safe and feasible with the advantages of mini-invasive and quick recovery.

Objective To evaluate the relationship between myocardial perfusion imaging quality and reconstruction time of dual-souce CT (DSCT).Methods Myocardial perfusion imaging was performed in 28 subjects using second-generation DSCT.The coronary arteries of all selected subjects were normal.280 ms temporal resolution was used,and the image of 30 ％-80 ％ R-R phase was reconstructed by retrospective ECG gating interval 5 ％.The artifact area of myocardial perfusion iodine map image of each R-R interval were obtained.Average segment artifacts of the heart bottom,central,apical,apical level of heart level were calculated and statistical analyzed.Results The artifact area of myocardial perfusion iodine map of the heart bottom,central,apical,and the whole heart had statistically significant differences (all P＜0.01),and the minimum artifact area was in60％ R-R phase ([0.31±±0.28]cm2,[0.18±0.23]cm2,[0.13±0.13]cm2,[0.22± 0.18]cm2).There was no difference between different phases of the heart apical level (P=0.634).The minimum artifact area of myocardial perfusion iodine map of the heart bottom,central,apical,apical level in 60％ R-R phase at the heart apical,the difference had statistically significant (F 3.701,P=0.014),there was no difference between the heart apical and central (P＞0.05),but the difference between the heart apical and other parts had statistically significant (P＜0.05).Conclusion Using 280 ms temporal resolution,second-generation DSCT can achieve the optimal myocardial perfusion imaging quality using 60％ R-R phase reconstruction.

Objective To investigate the diagnostic value of dual-energy CT virtual non-contrast (VNC) technology for osteoporosis(OP). Methods Dual-energy CT images of 50 patients with lumbar traumas were collected prospectively.Patients who suffer from vertebral bodies fractures between lumbar 1 to 4, have internal metal fixations or underwent percutaneous vertebroplasty, or presented tumors or compromised bone metabolism induced by diseases or medications were excluded.The scanning range was from the upper edge of the 12th thoracic vertebral body to the lower edge of the first sacral vertebral body. The voltages of tubes A and B were 90 kV and Sn 150 kV,and the reference tubes currents were 220 mAs and 138 mAs. Image reconstruction was performed using Advanced Modeled Iterative Reconstruction (ADMIRE)with iterative strength of 3 and convolution kernel of Qr 40.The default parameters of the virtual non-contrast software were corrected by the standard recommended by the Bone Marrow software of the post-processing platform Syngo.via,and the CT value of calcium(contrast media CM),the CT value of mixed energy images(regular CT value,rCT),the calcium density(CaD)and the fat fraction(Fat)were measured. The bone mineral density (BMD) and T score of each lumbar vertebra from lumbar 1 to lumbar 4 were measured by dual energy X-ray absorptiometry(DXA).With T score less than or equal to the 2.5 standard deviation as the gold standard for the diagnosis of OP,correlations between CT measurements and vertebral BMDs were analyzed using Pearson correlation analysis and linear regression and the diagnostic values of different CT measurements for OP were compared using receiver operating characteristic curve. Results Each of the vertebral bodies was analyzed as a single unit.Fifty of them were osteoporotic and the rest 116 were non-osteoporotic.Except for Fat,the CT measurement parameters of the osteoporotic vertebral bodies were lower than those of the ones without osteoporosis, and the difference was statistically significant (P<0.01).CM,rCT and CaD were significantly correlated with BMD(r were 0.75,0.65,0.71,all P<0.01)and there was a linear relationship(F were 209.91,120.24,167.69,all P<0.01).Meanwhile,CM,rCT,CaD and T score were also significantly correlated (r were 0.74, 0.65, 0.70, all P<0.01) with a linear relationship (F were 195.04,120.29,156.37,all P<0.01).CM,rCT and CaD had relatively high concordance rates against the OP diagnosis gold standard (respectively 81.9%, 62.2% and 81.9%). CM and CaD had higher concordance rates than rCT,the difference being statistically significant(P<0.01),and by the CM less than 239.5 HU or CaD less than 10.9 mg/cm3standard, their sensitivities of diagnosing osteoporosis were respectively 86.0% and 84.0%,while the specificities,80.2% and 81.0%.After superimposing CM and CaD, the results did not improve the diagnosis efficiency of OP (pre-superposition diagnostic performance better than post-superposition (P<0.05). Conclusion The VNC technology on DECT can do both vertebral fractures diagnosis and osteoporosis assessment at the same time, thus optimizing the clinical examination process.

Objective To investigate the diagnosis and treatment of mucin-producing intrahepatic biliary tumor (MPIBT).Methods We retrospectively analyzed the clinical,radiologic,surgical and pathologic findings of 16 MPIBT cases from January 2004 to December 2011.Results There were six men and ten women,age ranged from 44 to 69 years (mean 60 years).Clinical presentation included jaundice with abdominal dull pain in 5 patients,acute cholangitis in 4 patients,painless jaundice in 2 patients,upper abdominal dull pain in 3 patients,no obvious symptoms in 1 patient,body weight loss more than 5 kg within 3 months in 5 patients.The most characteristic appearance of MPIBT on magnetic resonance cholangiopancreatography were asymmetry of intrahepatic bile duct dilatation and the dilatation in both extraand intrahepatic bile duct distal to the hepatic mass and not sudden interruption in extrahepatic bile duct.The primary tumor located in the left hepatic bile duct in 15 cases,in the right hepatic bile duct in one.13 MPIBT cases received hemihepatectomy and extrahepatic bile duct resection and Roux-en-Y anastomosis was done in 8 cases,3 received palliative biliary drainage.Pathologically 13 was papillary adenocarcinoma and 3 was papillary adenoma.The 1-,2-,3-year survival rates for the 16 MPIBT patients were 81％,66％,56％,respectively.Conclusions MPIBT had no specific clinical manifestations,MRCP might be an effective means for the diagnositic strategy and assessment of tumor extension before surgery,radical resection was the first choice of treatment,palliative biliary drainage could prolong the survival time.

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.

This study is to examine the effects of NNIspm-mediated cellular senescence of HepG2 cells and elucidate its potential molecular mechanism. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution, intracellular fluorescence intensity and accumulation of intracellular reactive oxygen species (ROS) were detected by high content screening (HCS). Protein expression was detected by Western blotting. Polyamines content was analyzed by high performance liquid chromatography (HPLC). The results demonstrated that NNIspm significantly induced HepG2 cells senescence. This effect was due to the decrease of intracellular polyamines, the arrest at G0/G1 phase and an increase of ROS level. The molecular senescence marker p21 increased significantly after NNIspm treatment. In contrast, the protein expressions of Cyclin E and CDK2 were obvious down-regulation. The results indicated that cellular senescence induced by NNIspm was one of its antitumor mechanisms.

Objective To investigate kupffer cells (KCs) expressing indoleamine 2,3-dioxygenase(IDO)in the inhibition of allogeneic T-cell proliferation in vitro. Methods Real-time PCR was used to investigate the expression of IDO mRNA and FasL mRNA in KCs pretreated with or without IFNγ. High performance liquid chromatography was used to analyze the catabolism of tryptophan by IDO from KCs. Allogeneic T-cell response was used to confirm the inhibition of KCs in vitro. The proliferation of lymphocytes was detected using [3 H] thymidine incorporation. Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay. Results Real-time PCR revealed IDO mRNA and FasL mRNA expression in KCs pretreated with IFN-γ. IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KCs expressing IDO and FasL from BABL/c mice acquire the ability to suppress the proliferation of T-cells from C57BL/6, which could be blocked by the addition of 1-methyl-tryptophan and anti-FasL antibody. The co-cultured T-cells with KCs expressing IDO and FasL could induce allogeneic T-cell apoptosis and exhibited cell-cycle arrest in G1. Conclusion In addition to the Fas/FasL pathway, IDO may also play an important role in KCs to inhibit allogeneic T-cell proliferation in vitro.

The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.