Objective Several previous studies have shown androgens deficiency in men with CHF, and 2 studies on the prognostic significance of serum levels of androgens in CHF patients have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. Methods A total of 175 elderly (age≥60 years) men with CHF were recruited. Total testosterone (TT) and sex hormone binding globulin (SHBG) were measured, and free serum testosterone (eFT) was calculated. The median follow-up time was 1262 days. Results During follow-up 54 (30.9%) patients died. TT and eFT deficiency was found in 21.7% (38/175) and 27.4% (48/175) patients, respectively. Both TT and eFT were inversely associated with LVEF and NT-proBNP (all P<0.01). Kaplan-Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate (both P<0.01 by log-rank test). However, after adjustment for clinical variables, there were no significant associations between either TT or eFT levels or survival time (OR=0.97, 95% CI, 0.84-1.12, P=0.28; and OR=0.92, 95% CI, 0.82-1.06, P=0.14, respectively). Conclusion Our study showed that although levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, they are not independent predictors for mortality.

Objective:To develop a deep convolutional neural network (CNN) to automatically detect gastric lesions in endoscopic images.Methods:A CNN-based diagnostic system was constructed based on ResNet-34 residual network structure and DeepLabv3 structure, and trained by using 17 217 routine gastroscopy images.These images were from 1 121 gastric lesions of five types acquired in Peking University People′s Hospital between 2012 and 2018, namely peptic ulcer (PU), early gastric cancer (EGC) and high-grade intraepithelial neoplasia (HGIN), advanced gastric cancer (AGC), gastric submucosal tumors (SMTs), and normal gastric mucosa without lesions. The trained CNN was evaluated through a test dataset that contained 1 091 routine gastroscopy images of 237 gastric lesions. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CNN were calculated.Results:The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CNN-assisted diagnosis of EGC and HGIN were 78.6% (33/42), 84.4% (27/32), 60.0% (6/10), 87.1% (27/31), and 54.5% (6/11), respectively. The accuracy, sensitivity, and specificity of CNN-assisted diagnosis of PU were 90.4% (47/52), 92.7% (38/41), and 81.8% (9/11), respectively, the outcomes of AGC were 88.1% (52/59), 91.8% (45/49), and 70.0% (7/10), respectively, and those of gastric SMTs were 86.0% (43/50), 89.7% (35/39), and 72.7% (8/11), respectively. The CNN′s recognition time for all images of the test set was 42 seconds.Conclusion:The constructed CNN system, as a rapid and accurate auxiliary diagnostic instrument, can detect not only EGC and HGIN but also other gastric lesions.

Objective To summarize the current status and trend of hypoglycemic agents of diabetic inpatients in different departments of Chinese PLA General Hospital.Methods The clinical data of diabetic patients admitted to Chinese PLA General Hospital from January 2000 to May 2014 were collected(those hospitalized in the department of endocrinology were excluded).A total of 10 041 patients were selected by stratified random sampling.The type of hypoglycemic agents in different departments and the variation on anti-hyperglycemic drugs with time were retrospectively analyzed.Results Of all the patients in non-endocrinological wards, 50.2% were treated with insulin, 36.9% with metformin, 21.3% with α-glycosidase inhibitor, and 18.9% with sulfonylureas.Metformin, α-glucosidase inhibitors, pre-mixed 30R, and insulin glargine were more commonly used than other anti-hyperglycemic agents, accounting for 36.9%, 21.0%, 14.0%, 8.7%, respectively.Metformin, sulfonylureas, α-glucosidase inhibitor, and different types of insulin were more widely applied in internal medicine while insulin therapy was more frequently used in surgical department.During the past 15 years, the proportions of insulin, glinides, α-glucosidase inhibitor, and thiazolidinediones application were gradually increased, while the proportions of sulfonylureas and metformin treatment were on the decline trend.Conclusion Most of the inpatients were treated with oral antidiabetic drugs.Metformin, α-glucosidase inhibitor, pre-mixed 30R, and insulin glargine were the most frequently prescribed agents for the inpatients.

Objective To assess the significance of insulin tolerance test(ITT) in clinical diagnosis of adult growth hormone deficiency(GHD).Methods Eighty-two patients with an established diagnosis of adult GHD [53males,29 females,mean age (30.9 ± 12.3) years (18-65 years)] were reviewed retrospectively for evaluating the GH response to ITT in the General Hospital of the People' s Liberation Army.Control data for peak GH after ITT were obtained in 15 healthy subjects [9 males,6 females,mean age (26.7 ± 5.6) years (22-41 years)].Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the diagnostic cut-off point of peak GH and GH increment response to ITT.Results (1) Mean peak GH response to ITT was significantly higher in 15 controls compared with 82 patients (the median 14 μg/L vs 0.62 μg/L,P =0.001).The cut-off point of the peak GH(chemiluminescent immunoassay,CLIA) response to ITT in adult GHD was 4.935 μg/L (AUC 0.993).(2) Mean GH increment was significantly higher in 15 controls compared with 82 patients (the median 13.17 μg/L vs 0.19 ug/L,P＜0.001).The cut-off point of the GH increment was 4.088 μg/L(AUC 0.937),with a 91.5％ sensitivity and 100％ specificity.(3) The peak GH showed even higher diagnostic value than the GH increment after ITT.(4)The above mentioned cut-off points (peak GH less than 4.935 μg/L and 5 μg/L) had a coincidence with a 95.1％ sensitivity and 100％ specificity,respectively.Conclusion The current guidelines for the diagnosis of adult GHD based on the optimal cut-off point of the peak GH(CLIA) response to ITT less than 5 μg/L turned to be of reliable diagnostic value in our country.

Objective To explore the serum level of vascular endothelial growth factor (VEGF) of the patients with asymptomatic and symptomatic peripheral artery disease (PAD) in diabetics for providing evidence for screening the patients with PAD early. Methods Selected the study population including diabetics without PAD(90 cases),diabetics with asymptomatic PAD patients(93 cases)and diabetics with symptomatic PAD patients(92 cases). The level of serum VEGF was measured using enzyme linked immunosorbent assay(ELISA) and analyzed in the three groups. The varia-tion of serum VEGF was further analyzed in the three groups excluding the diabetic retinopathy in the stratified analysis. Results The serum level of VEGF with asymptomatic and symptomatic PAD in diabetics were increased,compared with the diabetics without PAD (P<0.05). Excluding the patients with diabetic retinopathy, the serum level of VEGF of the patients with asymptomatic and symptomatic PAD in diabet ics was still increased, compared with the dia betics without PAD (P<0.05). The serum level of VEGF level was significantly positively associated with HbA1c in the pa-tients with asymptomatic and symptomatic PAD in diabetics (r=0.267, 0.352, P all<0.05). Conclusion The level of serum VEGF in the patients with asymptomatic and symptomatic PAD in diabetics had been significantly increased.

Objective:To study the impact of different scattering correction algorithms in the reconstruction of PET/CT images on image artifacts and the precision of quantitative parameters.Methods:The phantom as described in the National Electrical Manufacturers Association (NEMA) NU2 standard was filled with 18F. The background activity was fixed, and the activity of the solution in the spheres was adjusted to obtain several configurations, including the normal ratio group (4.08∶1) and the extreme ratio group (200∶1). The surface contamination group with the same ratio as the extreme ratio group contained a small radioactive source with different doses of 18F (74, 37, 3.7 and 0.37 MBq) placed at the surface of the phantom. PET/CT images of 30 patients (21 males, 9 females, age: (44.5±10.2) years) from Peking University Cancer Hospital & Institute between July 2012 and December 2021 were retrospectively analyzed, including 10 with normal images ( 18F-FDG) and 20 with abnormal images (10 with dislocation during acquisition, 10 with surface contamination). The images were reconstructed with relative and absolute scattering correction. The phantom was evaluated using the target to background ratio (TBR) and the artifact classification. CV as well as the artifact classification were used to compare the clinical image quality. Mann-Whitney U test and χ2 test were used to analyze data. Results:In the normal ratio group and the extreme ratio group, the TBRs of phantom images reconstructed with relative correction were significantly higher than those with absolute correction (normal ratio group: 3.30(1.94, 4.53) vs 2.72(1.56, 3.56); z=-2.20, P=0.028; extreme ratio group: 105.47(45.62, 162.82) vs 101.36(43.96, 155.57); z=-1.99, P=0.046). In the surface contamination group, with the increase of the activity of the small source, the artifact became more obvious, and the artifact classification score of absolute correction was significantly better than that of relative correction (1.5(1.0, 2.0) vs 2.5(2.0, 3.0); z=-2.00, P=0.046). In the 10 normal 18F-FDG PET/CT patients, the CVliver of the relative correction (9.67%(8.00%, 11.00%)) was significantly lower than that of absolute correction (11.00%(9.00%, 12.00%); z=-2.57, P=0.010), indicating the higher image quality of images with relative correction. In abnormal images, the image quality of absolute correction was significantly higher than that of relative correction with fewer and less severe artifacts (dislocation cases: 9/10 vs 4/10; χ2=5.50, P=0.019; surface contamination cases: 9/10 vs 4/10; χ2=5.50, P=0.019). Conclusions:The relative scattering correction is suitable for normal situations in clinical PET acquisition. However, with dislocation or surface contamination, the absolute scattering correction helps to reduce the artifacts and improve the image quality.

BACKGROUNDBone marrow hematopoietic function suppression is one of the most common side effects of chemotherapy. After chemotherapy, the bone marrow structure gets destroyed and the cells died, which might cause the hematopoietic function suppression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that associates with cell proliferation and resistance to apoptosis. The aim of this study was to restore or resist the bone marrow from the damage of chemotherapy by the HO-1 expression of mouse mesenchymal stem cells (mMSCs) homing to the mice which had the chemotherapy-induced bone marrow suppression.

METHODSOne hundred and sixty female Balb/c mice (6-8-weeks old) were randomly divided into four groups. Each group was performed in 40 mice. The control group was intraperitoneally injected for 5 days and tail intravenously injected on the 6th day with normal saline. The chemotherapy-induced bone marrow suppression was established by intraperitoneally injecting cyclophosphamide (CTX) into the mice which performed as the chemotherapy group. The mMSCs were tail intravenously injected into 40 chemotherapically damaged mice which served as the mMSCs group. The difference between the HO-1 group and the mMSCs group was the injected cells. The HO-1 group was tail intravenously injected into the mMSCs that highly expressed HO-1 which was stimulated by hemin. The expression of HO-1 was analyzed by Western blotting and RT-PCR. Cell proliferation was measured using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Histopathologic examinations were performed 1 week after injection.

RESULTSCompared with the control group, the expression levels of HO-1 mRNA and protein were significantly higher in the HO-1 group (all P < 0.05), even obviously than the mMSCs group. CTX treatment induced apoptosis and inhibited proliferation. After injected, the white blood cell (WBC), red blood cell (RBC) and platelet (PLT) declined fast and down to the bottom at the 7th day. The bone marrow structure was destroyed incomplete. In vitro, the survival rate of cells in chemotherapy group was less than 50% after 24 hours. In contrast, mMSCs could do a favor to the cellular cleavage and proliferation. They slowed down the cell mortality and more than 50% cells survived after 24 hours. The effects of blocking apoptosis and bone marrow recovery could be more effective in the HO-1 group. In the HO-1 group, it had observed that the bone marrow structure became complete and the hemogram closed to normal at 7th day.

CONCLUSIONSHO-1 played an important role in promoting the recovery of CTX-induced hematopoietic damage. We suggest that HO-1 is able to restore the functions of chemotherapy-induced hematopoietic damage.

Animals ; Apoptosis ; drug effects ; Blood Platelets ; drug effects ; Blotting, Western ; Bone Marrow ; drug effects ; enzymology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclophosphamide ; toxicity ; Erythrocytes ; drug effects ; Female ; Heme Oxygenase-1 ; genetics ; metabolism ; Leukocytes ; drug effects ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; enzymology ; physiology ; Mice ; Mice, Inbred BALB C ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To estimate the renal absorbed dose in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE and to assess the radiation safety and guide the treatment. Methods:The dosimetric calculations of patients treated with 177Lu-DOTA-TATE were carried out based on planar images of single photon emission computed tomography (SPECT). The regions of interest (ROIs) of the whole body and kidneys were delineated and converted into activity. Accordingly, the time-activity curves of the ROIs were obtained. The effective half-lives and cumulative activity of ROIs were calculated through the fitting of a single exponential equation of the ROIs. Then the absorbed doses were calculated based on the medical internal radiation dosimetry (MIRD) formalism. Results:A total of 11 patients with neuroendocrine tumors received 18 cycles of treatments with 177Lu-DOTA-TATE. The effective half-lives of 177Lu-DOTA-TATE in the whole body and kidneys were 20.0-99.8 h and 38.2-75.2 h, respectively, with an average of (57.3 ± 21.4) h and (53.1 ± 12.5) h, respectively. The renal absorbed doses of 177Lu-DTA-TATE were 0.25-1.48 mGy/MBq, with an average of (0.90 ± 0.31) mGy/MBq. The minimum and maximum renal absorbed doses in a single treatment cycle were 1.8 Gy and 9.6 Gy, respectively, while the maximum renal absorbed dose in multiple treatment cycles was 21.7 Gy. Conclusions:The renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE were estimated. The result indicate that the renal absorbed doses were lower than the tolerable dose limits. This study is expected to guide the precise treatment of neuroendocrine tumors.

Santalene and santalol are the main components of valuable perfume sandalwood essential oil, and have good antibacterial, anti-oxidation and anti-tumor activities. Commercial sandalwood essential oil is mainly extracted from sandalwood tree that grows slowly and is difficult to cultivate. In addition, the extraction recovery of sandalwood essential oil from sandalwood tree is too low to meet the market demand. These factors make sandalwood essential oil expensive. An option is to use genetic engineering and molecular biological methods to heterologously express related synthase of santalene and santalol in microbial host. In this paper, the biosynthesis progress of santalene and santalol synthase, as well as the optimization of mevalonate metabolic pathways in the hosts are summarized. Furthermore, the strategies of applying protein engineering technology to carry out orthomutation of santalene synthase were also discussed, to provide reference for the optimal biosynthesis of santalene and santalol.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.