Objective To study the clinicopathologic features,effective therapeutic regimen and prognosis of human immunodeficiency virus (HIV) infection with acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML).Methods Two cases of HIV infection concurrent with leukemia,one with APL,one with CML,were studied and relevant literatures were reviewed.Results Case 1 was HIV infection concurrent with APL,ATO was used to induce remission,in the eight day of therapy,the patient died of brain disorder.Case 2 was HIV infection concurrent with CML,hydroxycarbamide and interferon were used to induce remission,three month later,state of an illness progressed to acute phase,after combination chemotherapy,concurrent with lung multiple infection (fungus and pneumocystis carinii),at last,the patient died of respiratory failure.Conclusion HIV infection concurrent with acute and chronic leukemia has poor therapeutic effect,and is easy to infect seriously.

Objective To evaluate the role of adenosine A1 receptors in hippocampal neurons in the cognitive dysfunction caused by isoflurane anesthesia in aged mice.Methods Sixteen male adenosine A1 receptor gene knockout homozygote mice (gene knockout mice) and 16 male wild-type mice,aged 18-22 months,weighing 27-32 g,were studied.Each type of mice was randomly divided into 2 groups (n=8 each) using a random number table:control group (group C) and isoflurane anesthesia group (group Ⅰ).Mice inhaled 1.4％ isoflurane in 100％ O2 for 2 h in group Ⅰ,and 100％ O2 for 2 h in group C.All the mice underwent Morris water maze test at 24 h after isoflurane or O2 inhalation.After the test,the mice were sacrificed and the hippocampal tissues were harvested to determine the number of β-amyloid1-42 (Aβ1-42) plaques (using immunohistochemistry) and expression of phosphorylated tau (p-tau) protein,and 2B subunit-containing N-methyl-D-aspartate receptors (NR2B) (by Western blot analysis).Results Compared with group C of wild type mice,the escape latency was significantly prolonged,the number of Aβ1-42 plaques was enlarged,the expression of p-tau protein was up-regulated,and the expression of N R2B was down-regulated in group Ⅰ of wild type mice.Compared with group Ⅰ of wild type mice,the escape latency was significantly shortened,the number of Aβ1-42 plaques was decreased,the expression of p-tau protein was down-regulated,and the expression of NR2B was up-regulated in group Ⅰ of gene knockout mice.There was no significant difference in the parameters mentioned above between group Ⅰ and group C of gene knockout mice.Conclusion Adenosine A1 receptors in hippocampal neurons mediate isoflurane anesthesia-induced cognitive dysfunction in aged mice,and the mechanism may be related to promotion of deposition of Aβ,phosphorylation of tau protein and inhibition of activities of NR2B.

OBJECTIVE To investigate the effect of curcumin on proliferation of neural stem cells (NSCs) of rats and the mechanism. METHODS NSCs derived from the forebrain of rat E15 embryos were cultured in vitro and identified by neuroepithelial stem cell protein ( nestin and SOX2) staining. NSCs were treated with curcumin 0.1, 0.5, 2.5, 12.5 and 62.5 μmol.L-1 for 24 h, respectively. The cyto-toxicity was estimated by measuring the release of lactate dehydrogenase(LDH). Cell viability and prolif-eration were analyzed respectively by MTT and BrdU assay. The mRNA expression levels of glucocorti-coid receptor (GR), Stat3, Notch1 and p21 were detected by qRT-PCR. The protein expression levels of total GR, Stat3 and phosphorylated Stat3 were measured by Western blotting. RESULTS The primary neural stem cells were identified as NSCs. Curcumin 12.5 and 62.5 μmol.L-1 had cell cytotoxicity( P<0.05). Cell viability assay indicated that curcumin 0.5 and 2.5 μmol.L-1 enhanced NSCs viability( P <0.05), but in 62.5 μmol.L-1 group the cell cytotoxicity was inhibited(P<0.05). Curcumin 0.1, 0.5 and 2.5 μmol.L-1 increased NSCs proliferation ( P < 0. 05), whereas 12. 5 and 62. 5 μmol.L-1 caused a decrease in NSCs proliferation(P<0.05). The mRNA expression level of GR in 0.5 μmol.L-1 group was significantly reduced( P<0.05). Western blotting analysis revealed that the protein expression of GR, Stat3 and p-Stat3 was inhibited by curcumin in 0.5 μmol.L-1 group(P<0.05). CONCLUSION Curcumin stimulates NSCs proliferation, possibly by inhibiting GR mRNA and related protein expression.

Objective To explore the clinical value of MCV combined with Hb electrophoresis in detection of tha-lassemia. Methods Selected 150 cases of patients with thalassemia as the observation group, and other 150 cases of non-thalassemia patients were selected in our hospital as control group. MCV and Hb electrophoresis examination were conducted in two groups of patients, and the positive rates were recorded. And then we analyzed the specificity and sensitivity of the two methods as well as the combined examination. Results In the single MCV or Hb electrophoresis detection, the positive rate in observation group patients was higher than this in the control group, and the differences were statistically significant (P<0.05). The sensitivity and specificity of MCV detection were separately 91.33% and 76.67%, and the sensitivity and specificity of Hb electrophoresis were separately 85.33% and 79.67%. And when we conducted the combined detection, the sensitivity decreased, but the specificity increased. Conclusion For the patients with thalassemia, by using the method of MCV combined with Hb electrophoresis, we can improve the specificity in de-tection of disease. It is worthy of promotion in clinical use.

Objective: To investigate the expression characteristics of Tim-3 on natural killer (NK) cells of peripheral blood in patients with acute myeloid leukemia (AML) and its clinical significance. Methods: Peripheral blood was obtained from 39 patients with newly diagnosed AML before intervention, with peripheral blood from 28 cases of healthy volunteers collected as normal control. Using CD3, CD56 and Tim-3 as markers, expression levels of Tim-3 on the peripheral blood NK cells were detected by immune fluorescence labeling and flow cytometry. Results: The ratio of the peripheral blood CD3^-CD56⁺ NK cells in newly diagnosed AML patients (5.74±5.31) %decreased significantly, compared with the normal control (12.55±6.33) % (t=4.596, P<0.001) . Tim-3 expression on the peripheral blood NK cells in newly diagnosed AML patients (42.67±19.08) % decreased significantly, compared with the normal control group (60.99±20.69) % (t=3.781, P<0.001) . CD3^-CD56⁺NK cell ratio of peripheral blood in AML patients was significantly correlated with Chromosome karyotype (t=2.915, P<0.005) . Expression level of Tim-3 on NK cells in the peripheral blood of AML patients had significant correlation with ratio of CR and NCCN high risk group (P<0.05) . Conclusion The rate of NK cells in peripheral blood and the expression level of Tim-3 on NK cells in AML patients decreased significantly.The lower expression level of Tim-3 on NK cells correlate with prognosis of AML.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

SARS-CoV-2 main protease (M^pro) is one of the most extensively exploited drug targets for COVID-19. Structurally disparate compounds have been reported as M^pro inhibitors, raising the question of their target specificity. To elucidate the target specificity and the cellular target engagement of the claimed M^pro inhibitors, we systematically characterize their mechanism of action using the cell-free FRET assay, the thermal shift-binding assay, the cell lysate Protease-Glo luciferase assay, and the cell-based FlipGFP assay. Collectively, our results have shown that majority of the M^pro inhibitors identified from drug repurposing including ebselen, carmofur, disulfiram, and shikonin are promiscuous cysteine inhibitors that are not specific to M^pro, while chloroquine, oxytetracycline, montelukast, candesartan, and dipyridamole do not inhibit M^pro in any of the assays tested. Overall, our study highlights the need of stringent hit validation at the early stage of drug discovery.

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.