[Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma].

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

[Association of urinary sodium excretion with fluid overload in patients with chronic kidney disease].

Objective: To investigate the relationship between urinary sodium excretion and fluid overload (FO) in non-dialysis patients with chronic kidney disease (CKD). Methods: Patients with CKD stage 1-4 who underwent bioelectrical impedance (BIA) in the Department of Nephrology, Jiangsu Province Hospital from December 2019 to January 2021 were recruited. All enrolled patients were categorized into two groups according to whether or not they develop FO. Further, clinical parameters were compared between the two groups. Spearman correlation analysis was used to investigate the association between over hydration/extracellular water (OH/ECW) and clinical characteristics. Multivariate logistic regression analysis was performed to evaluate the relationship between urinary sodium excretion and FO (FO was defined as OH/ECW≥7%). Results: A total of 385 patients with CKD stage 1-4 were finally included in the study, with a mean age of (46±15) years. There were 216 male cases (56.1%), and 150 cases (39.0%) existed FO. Spearman correlation analysis indicated that OH/ECW positively correlated with urinary sodium excretion (r=0.147, P=0.004), urinary protein excretion (r=0.555, P<0.001) and systolic blood pressure (r=0.241, P<0.001), but inversely related to estimated glomerular filtration rate (eGFR) (r=-0.111, P=0.030) and serum albumin (r=-0.659, P<0.001). After adjusting for confounding factors including age, systolic blood pressure, diabetes, urinary protein excretion, serum albumin, serum sodium, serum chlorine, urinary calcium excretion, urinary phosphorus excretion and use of diuretics, multivariate logistic regression analysis demonstrated that higher level of urinary sodium excretion was associated with increased risk of FO in patients with CKD (OR=1.005, 95%CI: 1.000-1.011, P=0.048). Conclusion: High urinary sodium excretion is independently associated with fluid FO in non-dialysis patients with CKD.

Expression of CD63 in Lung Tissue of Guinea Pigs Dying of Anaphylactic Shock.

ABSTRACT: Objective To study the protein expression of cluster of differentiation 63 （CD63） in lung tissues of guinea pigs that died of anaphylactic shock and discuss the diagnostic value of CD63 for death from anaphylactic shock. Methods Twenty guinea pigs were randomly divided into control group, anaphylactic shock immediate death group, cold storage group （4 ℃ for 48 h） and frozen group （-20 ℃ for 7 d）. The animal model of guinea pigs that died of anaphylactic shock was established with human mixed serum injection. The expression changes of CD63 protein and CD63 mRNA in lung tissues were detected by hematoxylin-eosin （HE） staining, immunohistochemical staining, Western blotting, enzyme-linked immunosorbent assay （ELISA） and real-time RT-PCR. Results HE staining results showed congestion, and edema of lung tissues, and eosinophil infiltration in the anaphylactic shock groups. Western blotting analysis results showed that the expression of CD63 protein in the lung tissues of guinea pigs that died of anaphylactic shock was significantly higher than that in the control group （P<0.05）. Comparison between the anaphylactic shock groups was made, and the differences had no statistical significance. The results of immunohistochemical staining and real-time RT-PCR were consistent with that of Western blotting. ELISA results showed that CD63 protein expression in the immediate death group was higher than that in the control group （P<0.05）. Conclusion The expression of CD63 protein and CD63 mRNA in the lung tissues of guinea pigs that died of anaphylactic shock is significantly enhanced. Animal carcasses which were put in cold storage for 48 h and frozen for 7 d do not affect the examination of the above indicators. CD63 protein is expected to become an auxiliary diagnostic indicator of death from anaphylactic shock.

[Application of IMA and H-FABP in Forensic Diagnosis of Sudden Cardiac Death].

Acute myocardial ischemia is the most common cause of sudden cardiac death. The diagnosis of early myocardial ischemia is a hot point in forensic medicine, which is also an early and important part for a prevention against myocardial infarction. This paper conducts a comprehensive discussion of the structure, function, clinical value and forensic medicine application prospect of ischemia modified albumin （IMA） and heart-type fatty acid binding protein （H-FABP), aiming to determine whether the two proteins can be used as biochemical detection indicators of early myocardial ischemia for the diagnosis of sudden cardiac death in forensic medicine.

[Synthesis and activities of 4-deoxy-4 beta-arylmehtylene sulfonylamido-4'-demethylpodophyllotoxins].

AIM: To find new anticancer drug based on the structure of podophyllotoxin. METHODS AND RESULTS: 4-Deoxy-4-beta-arylmethylenesulfonylamido-4'- demethylpodophyllotoxins were (1-15) synthesized and their antitumour activities against KB cells and L1210 leukemia cells were tested. CONCLUSION: These compounds are new compounds. Among them, compounds 2, 3, 8, 9, 11 and 12 showed antitumour activities. When halides exist on the aryl ring of substituted sulfonyl group, the corresponding compound has relatively higher activities. The stereo factor is important for the activities.

Logic operations based on single neuron rational model.

This paper focuses on phase analysis to explore the single neuron local arithmetic and logic operations on their input conductances. Based on the analysis of the rational function model of local spatial summation with the equivalent circuits for steady-state membrane potentials, the prototypes spatial summation with the equivalent circuits for steady-state membrane potentials, the prototypes of logic operations are constructed. A mapping from a partition of input conductance space into functionally distinct phases is described and the multiple mode models for logic operations are established. The transitions from output voltage to input conductance in logic operations are also discussed for the connections between neurons in different layers. Our theoretical studies and software simulations indicate that the single neuron local rational logic is programmable and the selection of these functional phases can be effectively instructed by presynaptic activities. This programmability makes the single neuron more flexible in processing the input information.

Single neuron local rational arithmetic revealed in phase space of input conductances.

We present a phase space analysis to explore the potential of single neuron local arithmetic operations on its input conductances. This analysis was conducted first by deriving a rational function model of local spatial summation by using the equivalent circuits for steady-state membrane potentials. It is shown that developed functional phases exist in the space of input conductances, where a single neuron's local operation on input conductances can be described in terms of a set of well-defined arithmetic functions. It is further suggested that this single neuron local rational arithmetic is programmable, in the sense that the selection of these functional phases can be effectively instructed by presynaptic activities. This programmability adds the degree of freedom in a single neuron's ability to process the input information.

[Synthesis and antitumor activity of 4-O-(halogenated) acyl-4'-demethylepipodophyllotoxin analogues].

A series of 4-(halogenated)acyl-4'-demethylepipodophyllotoxin analogues were conveniently synthesized by selective esterification in the presence of BF3.Et2O, and screened in vitro against L1210 leukemia and KB cells. Most of these compounds showed marked antitumor activity and exhibited more potent activity than that of etoposide.

[Synthesis and antitumor activity of 4-S-(5-amido-1,3,4-thiodiazol-2-yl)4-deoxy-4'-demethylepipodophyllotoxi n analogues].

By the condensation of 4'-demethylepipodophyllotoxin with 2-amino-5-mercapto-1,3,4-thiodiazole in CF3COOH and acylation in the presence of DEPC, 10 title compounds were conveniently synthesized. These compounds were screened in vitro against L1210 leukemia and KB cells, in which compounds SIPI-92-1772, 1774, 1775, 1776, 1777 and 1779 exhibited more potent anti-tumor activity.

[Synthesis and antitumor activity of 4-(2-amido-2-ethoxycarbonyl) ethylsulfenyl-4-deoxy-4'-demethylepipodophyllotoxin analogues].

Twenty three 4-(2-amido-2-ethoxycarbonyl) ethylsulfenyl-4-deoxy-4'-demethylepipodophyllotoxin analogues were synthesized by three steps, in which trifluoroacetic acid was used as a condensation agent of 4'-demethylepipodophyllotoxin with L-cysteine ethyl ester hydrochloride without any protection of phenolic hydroxy and amino groups. All compounds were screened in vitro against L1210 leukemia and KB cells, in which, compounds 11, 16 and 18 exhibited more potent antitumor activity than etoposide.

[Synthesis and antitumor activities of 4-acylamido-4-deoxy-4'-demethylepipodophyllotoxin analogues].

Twenty four 4-acylamidc-4-deoxy-4'-demethylepipodophyllotoxins were synthesized by acylation of 4-amino-4-deoxy-4'-demethylepipodophyllotoxin by means of usual methods, and screened in vitro. This type of compounds showed strong antitumor activities, most of them are superior to etoposide in the inhibition against L1210 and KB cells.

[Synthesis and antitumor activities of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues].

This paper describes the synthesis and antitumor activity of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues. 4-Mercapto-4-deoxy-4'-demethylepipodophyllotoxin prepared from 4'-demethylepipodophyllo-toxin with H2S in the presence of BF3.Et2O, was acylated with different acids using diethyl cyanophosphonate and thus, corresponding 4-acylthiol-4-deoxy-4'-demethyl epipodophyllotoxin analogues were synthesized. These compounds were screened in L1210 leukemia and KB cells, and one compound has activity similar to etoposide, and others were generally weaker than etoposide and corresponding 4-acylamido-4-deoxy-4'-demethylepipodophyllotoxin analogues.

[Synthesis and antitumor activity of 4-alkylthio-4-deoxy-4'-demethylepipodophyllotxin derivatives].

As a continuing part of our study on the chemistry and antitumor activity of podophyllotoxin, 11 new C-4 S-substituted podophyllotoxin derivatives were synthesised and screened in vitro against L1210 leukemia and KB cells. Thus, 4'-demethylepipodophyllotoxin was reacted with thiols in the presence of BF3. Et2O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-deoxy-4'-demethylepipodophyllotoxin, when reacted with thiols, also gave rise to corresponding thioether (4-alkylthio-4-deoxy-4'-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activity as etoposide in the inhibition against L1210 leukemia, and compounds 9, 10, 12 and 15 also have comparable activity with etoposide against KB cells.