Objective Calculus Bovis(CB)is a kind of valuable traditional Chinese medicine,which has been used in clinic for a long time.It has been shown to have significant anti-stroke,anti-inflammatory and anti-tumor effects.But its mechanism for treating Prostate cancer(PCa)remains unclear.The purpose of this study was to explore the target and mechanism of its action in the treatment of prostate cancer throμgh network pharmacology and in vitro and in vivo experiments.Methods The effective compounds of Calculus Bovis were collected by TCM pharmacology database and analysis platform(TCMSP).Search for potential compound targets in TCMSP.Search the Drμgbank,GeneCards,OMIM,PharmGkb,and TTD databases for disease targets associated with prost cancer.Disease and compound targets were integrated in the STRING database to construct their interaction network(PPI)to reveal the key targets of compound treatment for prostate cancer.In order to elucidate the mechanism of Calculus Bovis in the treatment of prostate cancer,GO functional enrichment and KEGG pathway enrichment analysis were conducted using Cytoscape software.The mechanism of treating prostate cancer with Calculus Bovis was studied in vitro and in vivo.Results A total of 11 compounds with anti-prostate cancer activity were identified.Oleanolic acid,ursolic acid,ergosterol,deoxycorticosterone,methylcholine and cholverdin were potential effective components.A total of 367 targets of Calculus Bovis compounds and 2152 targets of prostate cancer were found.The core targets of Calculus Bovis in the treatment of prostate cancer included TP53,STAT3,AKT1,HSP90AA1,ESR1,SRC,JUN,RELA,CCND1,CDKN1A,EGFR,AR,etc.The biological functions of Calculus Bovis mainly involve oxidative stress response,response to steroid hormones,cell response to chemical stress,peptide-serine modification and phosphorylation,and protein serine/threonine kinase activity.Calculus Bovis treatment of prostate cancer mainly involves PI3K-AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway,etc.In vitro and in vivo experiments showed that Calculus Bovis promoted apoptosis of PC3 cells of prostate cancer by inhibiting PI3K-AKT signaling pathway.Conclusion Calculus Bovis has a therapeutic effect on prostate cancer,and its function is related to inhibiting PI3K-AKT signaling pathway and promoting apoptosis of cancer cells.

Objective:To investigate the therapeutic effect and safety of low-dose dexitabine combined with DA/HA chemotherapy regimen in acute myeloid leukemia (AML) patients with moderate or poor prognosis.Methods:The clinical data of 25 initially diagnosed AML patients (non-acute promyelocytic leukemia) in Affiliated Hospital of Southwest Medical University from April 2013 to May 2020 were retrospectively analyzed. According to the National Comprehensive Cancer Network (NCCN) guideline, all patients were divided into moderate prognosis group (5 cases) and poor prognosis group (20 cases), and they were given low-dose decitabine combined with DA/HA regimen (decitabine 10 mg, day 1-10; daunorubicin 60 mg/m 2, day 1-3; homoharringtonine 2.5 mg/m 2, day 1-7; cytarabine 100-200 mg/m 2, day 1-7). The clinical efficacy and adverse reactions of both groups were observed. Results:Among 25 patients, 1 patient gave up during the treatment; 14 patients received 1 cycle of treatment and the complete response (CR) rate was 71.4% (10/14); 10 patients received ≥2 cycles of treatment and the CR rate was 70.0% (7/10); the difference of CR rate in patients with different treatment cycles was not statistically significant ( χ2 = 0.01, P > 0.05). In the moderate prognosis group, 4 cases achieved CR and 1 case had no response (NR), the CR rate was 80.0% (4/5), and the total effective rate was 80.0% (4/5). In poor prognosis group, 13 cases achieved CR, 4 cases achieved partial response (PR), 2 cases had NR, 1 case gave up the treatment, the CR rate was 68.4% (13/20), and the total effective rate was 89.5% (17/20). There were no statistical differences in the CR rate and the total effective rate between the two groups (both P > 0.05). The adverse reactions of all patients were mild and all patients could tolerate. Conclusions:Low-dose dexitabine combined with DA/HA regimen has a high remission rate in treatment of AML patients with moderate or poor prognosis, and the adverse reactions can be tolerated.

OBJECTIVETo identify the predictive factors for differentiating pancreatic ductal adenocarcinoma (PDAC) from other neoplastic solid pancreatic lesions and assess the accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis of PDAC.

METHODSWe retrospectively analyzed the clinical data of patients referred for EUS-FNA evaluation of pancreatic lesions in the Digestive Endoscopic Center of Nanfang Hospital between January, 2009 and May, 2016. The cases with unknown diagnosis, missing data, repeated punctures, cystic lesions and benign lesions were excluded from the analysis. The positivity rates of EUS-FNA were compared between patients with PDAC and those with non-PDAC lesions, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS-FNA were assessed in the diagnosis of PDAC. Univariate and multivariate logistic regression analyses were used to identify the factors for differentiating PDAC from non-PDAC lesions based on the demographic characteristics, clinical presentations, laboratory data, and endoscopic ultrasonography imaging features of the patients.

RESULTSAmong the 75 patients with solid neoplastic pancreatic lesions, 54 (72.0%) were found to have PDAC and 21 (28.0%) had non-PDAC lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA for the diagnosis of PDAC were 77.8%, 100.0%, 100.0%, 63.6% and 84.0%, respectively. No significant difference was found in the positivity rate of EUS-FNA between patients with PDAC and those with non-PDAC lesions (77.8% 76.2%, > 0.05). Multivariate regression analysis identified abdominal pain (=5.163, 95%: 1.093-24.389, =0.038), lesion size (=0.926, 95%: 0.877-0.978, =0.006), characteristics of the solid lesions (=7.105, 95%: 1.440-35.043, =0.016), and evidence of metastases (=6.165, 95%: 1.332-28.533, =0.020) as the independent factors for predicting PDAC.

CONCLUSIONSThe pretest characteristics including abdominal pain, evidence of metastases, and lesion size and lesion characteristics defined by endoscopic ultrasonography findings can reliably predict a diagnosis of PDAC. EUS-FNA has a high sensitivity and a high specificity for the diagnosis of PDAC.

Objective To analyze histomorphometrical characteristics of the bone and bone marrow tissues of the lumbar vertebrae in rabbits with fluoride treatment,and its correlation with signal intensity of MRI.Methods Forty New Zealand albino rabbits aged three months old were randomly divided into fluoride exposure of 30 cases and control of 10 cases,male and female,half each.One hundred milligrams of sodium fluoride were added to the municipal water each liter (fluoride content 100 mg/L) as drinking waterto fluorine for 180 days.Twenty-four of 30 cases with fluoride exposure had complete data (male10 casesand female14 cases).The same municipal water was used as control drinking water (fluoride content ＜ 0.9 mg/L).Eight of 10 cases with control had complete data (male andfemale in half).Twenty-four cases with fluoride treatment and complete data were classified into sensitive and resistant type according to the MRI signal intensity of the lumbar vertebra.Histomorphometrics of the vertebra and its correlation with the MRI signal intensity,and sensitivity in early diagnosis of osteofluorosis and feasibility of susceptibility to osteofluorosis detected with MRI were analyzed.Results Theratios of trabecular bone volume (BV),hematopoietic cell volume (HV) and fluid volume (FV) in bone marrow tissue to total cavernous tissue volume (TT) in group with fluoride treatment were 18.3％±2.6％,45.2％±6.0％ and 10.4％±5.7％ respectively.These were 14.5％±2.8％,36.3％±7.3％ and 6.2％±2.1％ in control group respectively.These parameters in fluoride group were significantly increased compared to control group.The ratio 26.0％± 8.0％ of adipocyte volume (AV) to TV in fluoride group was significantly lower than that 43.3％±5.6％ in control group.Two of 24 cases with fluoride exposure (8.3％,2/24) were sensitive and the remaining 22 (91.7％,22/24) were in resistance.The valuesof BV/TT,HV/TV and FV/TV were considered to be sensitive,resistant and control from large to small,while AV/TV value were opposite.A comparison resuhs of signal intensity in MRI showed that vertebra T1WI contrast to noise ratio (CNR) in the sensitive was the minimum (3.0±0.8),followed by resistance (21.3±3.8) andmaximum in the control (28.3±3.1),but CNR of FsT2WIwas opposite.There were positive associations between T1WI and AV/TV,FV/TV and BV/TV,and between FsT2WI and FV/TV and BV/ TV.There were inverse associationsbetween FsT2WI and AV/TV.Theoptimal threshold value of the vertebra T1WI CNR was 23.2 or lessin early diagnosis of skeletal fluorosis,with sensitivity of 83.3％ and specificity of 100％.FsT2WI was 5.7 or more,with sensitivity of 45.8％ and specificity of 100％.Conclusion The pathogenesis of osteofluorosis is relative to changes in bone marrow microenvironment and cells number in bone marrow tissue,and is correlated to MRI signal intensity.

Objective To investigate the diagnostic value of endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA) on malignant lesions in gastrointestinal adjacent tissue, and further to analyze the risk factors influencing positive rate of EUS-FNA. Methods The clinical data of 171 patients undergoing EUS-FNA from January 2009 to May 2016 were collected. The lesion location, size and characteristics, the number of needle passes, puncture suction negative pressure, size of puncture needle, and years of operator experience in EUS were retrospectively analyzed. Results The overall sensitivity, specificity, and accuracy of EUS-FNA in the diagnosis of malignant lesions were 78. 3％ ( 83/106) , 100. 0％ ( 65/65) , and 86. 5％( 148/171) , respectively. The univariable logistic regression analysis demonstrated that the risk factors of EUS-FNA were lesion location, lesion characteristics, and lesion size. In multivariate analysis, larger lesion size ( OR=1. 029, 95％CI: 1. 011-1. 047, P=0. 001) and lesion characteristics of solid ( OR=5. 098, 95％CI:1. 324-19. 633, P=0. 018) were independent factors affecting the positive rate of EUS-FNA. Among 171 cases performed by EUS-FNA, the incidence of postoperative complications was 1. 75％ ( 3/171 ) included 2 cases of fever and 1 case of acute pancreatitis, which were improved after conservative treatment. Conclusion EUS-FNA is a safe and effective method of cytological and histological diagnosis with high accuracy and sensitivity, importantly in distinguish malignancy from benign lesion in gastrointestinal adjacenttissue. Positive rate of diagnosis on malignant lesions by EUS-FNA is positively correlated with lesion size, and EUS-FNA positive rate of solid malignant lesions is significantly higher than that of cystic lesions.

Objective To detect the effect of low-dose heparin on endothelial function by detecting the change of yon Willebrand factor (vWF) in blood plasma of patients with sepsis shock after treatment with low-dose heparin in order to observe organ function and prognosis of patients.Methods A total of 118 patients with sepsis shock were randomized into low-dose heparin group and control group.In addition to the routine treatment,the patients in low-dose heparin group were given low-dose heparin,while those in control group were not.The levels of APTT,PT,platelet (PLT) count,hepatic function and renal function were determined before and after treatment in two groups,and hemorrhagic events or other complications were recorded.The lengths of stay in ICU and in hospital,the days of mechanical ventilation and the rates of acute respiratory distress syndrome (ARDS),disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS) and 28-day survival rate in the two groups were documented.The levels of vWF in patients of two groups were determined by using immunoturbidimetry before and after treatment.Results The rates of DIC and MODS in low-dose heparin group decreased significantly after therapy (rate of DIC,10.6％ vs.26.7％,P ＜ 0.05;rate of MODS,19.3％ vs.32.0％,P ＜ 0.05).Hepatic function and renal function in low-dose heparin group were significantly improved than that in the control group (P ＜ 0.05),28-day survival rate in the low-dose heparin group was higher than that in the control group (78.3％ vs.69.1％,P ＜0.05),the differences between low-dose heparin group and control group were not statistically significant in the lengths of stay in ICU and hospital,the days of mechanical ventilation and the rate of ARDS (P ＞ 0.05).The differences in APTT,PT and PLT were not significant from pre-treatment to after treatment and between the two groups (P ＞ 0.05).The levels of vWF in low-dose heparin group decreased significantly after therapy rather than those in control group (P ＜ 0.05).Conclusions The endothelial function is improved in patients with sepsis shock after employment of lowdose heparin.Low-dose heparin alleviates the interaction between coagulation and inflammation,improves hepatic,renal and other important organs function,decreases the rate of MODS and increases 28-day survival rate patients with sepsis.The low-dose heparin therapy is a safe and promising treatment in sepsis patients without severe side effects.

Objective To evaluate (1,3)-β-D-glucan (BG) assay as an aid for invasive fungal infection (IFI) diagnosis in severe pneumonia patients (diagnosis followed 2007 American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) severe pneumonia standard).Methods BG antigenemia was measured by BG Assay Box.IFIs was classified according to the blood fungal laboratory reports.Results 558 patients (185 females,373 males,mean age 64.7) were included.41 patients were proven to be fungal infected to be classified in exposure group.BG assay mean value in exposure group and unexposure group were (568.53 ±796.57) pg/mL,(51.4 ±63.27) pg/mL,respectively.Patients in the exposure group had significantly higher BG assay value than patients in the unexposure group (P ＜0.05).For the cutoff 100 pg/mL recommended by manufacturer,the sensitivity,specificity,positive predict value and negative predict value of the BG assay were 92.7％,92.5％,49.4％ and 0.6％,respectively.Conclusion BG assay has positive clinical value in invasive fungal infection diagnosis in severe pneumonia patients.

Objective To explore whether hypertonic saline would partake in regulating Notch signaling in microglia in experimentally induced cerebral ischemic rats.Methods Male SD rats were randomly divided into sham group, cerebral ischemia group, normal saline group ( NS group ) , 10%hypertonic saline group (10%HS group) , the model of cerebral ischemia were established in all rats except the sham group by using middle cerebral artery occlusion ( MCAO) .After 2 hours of MCAO, the rats were through reperfusion for 24 h.In addition, rats in the normal saline group and 10% HS group were respectively treated with a continuous intravenous injection of normal saline (0.3 mL/h) and 10%HS (0.3 mL/h) by tail vein for 24 h.Immunofluorescence methods, RT-PCR and Western blot were used to detect the expression of Notch1 and intracellular Notch receptor domain ( NICD) .All data was analyzed by one-way analysis of variance ( ANOVA) , The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests.Differences were considered statistically significant if P<0.05.Results Immunofluorescence showed that the expression of Notch1 and NICD were significantly increased in the microglia around peri-ischemia area in cerebral ischemia group and normal saline group compared to sham group;the expression of Notch1 and NICD in the microglia around peri-ischemia area were significantly reduced in 10% HS group compared to ischemia group and NS group.RT-PCR showed that the mRNA expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 1.000 ± 0.076; ischemia group: 2.203 ±0.283; NS group: 1.616 ±0.185; P <0.01 ); however, it was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group:2.203 ±0.283; NS group: 1.616 ±0.185; 10%HS group: 1.202 ±0.177; P <0.05 ) .Western blot showed that the protein expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.290 ±0.079; ischemia group: 0.750 ±0.029; NS group:0.765 ±0.182;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.750 ±0.029; NS group:0.765 ±0.182;10%HS group:0.390 ±0.195;P<0.05 ) .The protein expression of NICD was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.401 ±0.196; ischemia group: 0.906 ±0.359; NS group:0.847 ±0.153;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.906 ±0.359; NS group:0.847 ±0.153;10%HS group:0.561 ±0.165;P<0.05 ) .Conclusion Our results suggest that HS markedly suppresses Notch signaling in microglia around the ischemia tissue area in experimental induced cerebral ischemic rats.

Objective To analyze histomorphometrical characteristics of bone and bone marrow tissue in the vertebral lamina of patients with osteofluorosis, and to explore the influencing factors on signal intensity in MRI. Methods Spinal MRI of 109 patients (57 men, 52 women;age range 32-80 years;mean age 52 years) with osteofluorosis from December 2001 to May 2012 was analyzed retrospectively, including 48 patients in cervical segment, 31 in thoracic segment and 30 in lumbar segment. 36 pa?tients (16 men, 20 women;mean age 51 years;age range 34-68 years) had undergone laminectomy and the vertebral lamina speci?mens were collected. The cervical MRI of 48 patients with matching gender and age (26 men, 22 women;mean age 51 years, age range 34-71 years) was selected as control group, who were from areas where fluorosis is not endemic. All patients were divided in?to vertebra low, medium and high signal groups according to T1WI of MRI. The vertebra signal to noise ratio measure and stan?dardization of signal intensity were performed. Osteosclerosis, osteoporosis and normal bone were differentiated under spinal X?ray plain film. Combined with histomorphometric analysis of vertebra lamina in 36 patients, correlation between MRI signal intensity, histomorphometric parameters of the vertebra lamina and influencing factors on signal intensity were studied. Results 77 pa?tients (70.6%, 77/109) had osteosclerosis indicated by appearance of spine under X?ray, 29 (26.6%, 29/109) osteoporosis and 3 (2.8%, 3/109) normal bone. T1WI of MRI showed 25 cases had low signal vertebra, 52 medium signal and 32 high signal. The ver? tebra SNR in patients with osteofluorosis was lower on T1WI, T2WI and short time inversion recovery (STIR) sequences, compared with control group. Those with a low versus high signal on T1WI had 6.04 times the odds of osteosclerosis (OR=6.04, 95%CI 2.44-14.91, P<0.001). Histomorphometry of vertebral lamina in 36 patients with osteofluorosis was performed, revealing that not only the trabecular bone volume had changed, but also did the adipocyte volume and hemopoietic cell volume in the bone marrow tis?sues. Compared with normal reference values, trabecular bone volume was significantly increased (47.7%± 13.3% vs. 14.7%± 4.3%) (P<0.001);adipocyte volume was significantly decreased (12.3%±9.1%vs. 50.5%±8.7%);hematopoietic cell volume was decreased (40.0%±7.0%vs. 42.5%±8.5%) (P=0.038). There were inverse associations between trabecular bone volume and adipo?cyte volume (r=-0.869, P<0.001), and between trabecular bone volume and T1WI (r=-0.851, P<0.001) found by Pearson correla?tion test. In contrast, there were positive associations between T1WI and adipocyte volume (r=0.927, P<0.001). Conclusion The vertebra T1WI signal intensity is decreased in patients with osteofluorosis, resulting from increase of trabecular bone volume and re?duction of adipocyte volume. The vertebra STIR signal intensity is decreased, mainly caused by increase of trabecular bone volume.

OBJECTIVETo evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy.

METHODSClinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis.

RESULTSThe median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors.

CONCLUSIONSNeck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Carcinoma ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; pathology ; Nasopharyngeal Neoplasms ; radiotherapy ; Neck ; Neck Dissection ; Neoplasm Recurrence, Local ; surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome