Progress of potential therapeutic targets and small molecule ligands of anti-colorectal cancer pathogenic Fusobacterium nucleatum / 药学学报

The composition of intestinal microflora is closely related to the occurrence and development of colorectal cancer (CRC). Among them, Fusobacterium nucleatum (Fn) has been proved directly related to the recurrence, metastasis and chemotherapy resistance of CRC. Therefore, it is of great significance for the prevention and treatment of colorectal cancer by the exploration potential anti-Fn drug targets and discovery small molecule drugs. However, no selective anti-Fn small molecule inhibitors have been reported so far as well as their anti-Fn thereby "anti-Fn further anticancer" mechanisms are unclear. Herein, this article reviews the potential therapeutic targets and small molecule ligands of Fn in order to provide a reference for the development of anti-Fn and anti-CRC small molecule drugs.

Effects of a simulated plateau environment on fracture healing in rats / 中华创伤骨科杂志

Objective:To study the effects of a simulated plateau environment on fracture healing in rats.Methods:A rat model of mid-femoral fracture was established by hacksaw truncation and intramedullary fixation with Kirschner wires in 60 male Wistar rats which were divide into 2 groups ( n=30) by the random number table method. The rats in the control group were raised in the animal experiment center of The 940 Hospital of Joint Logistic Support Force of Chinese PLA at an altitude of 1,400 m, while the rats in the plateau group were placed in an animal experimental cabin in a simulated plateau environment at a simulated altitude of 5,000 m. The body weight was weighed once a week and X-ray films were taken every 2 weeks. Blood samples were collected after 4 weeks for detection of biochemical indicators of bone metabolism. After 8 weeks, the femurs of the surgical side were taken for bone biomechanical detection and the bone mineral density of the healthy side was detected. After 4 and 8 weeks, the femurs of the surgical side were taken for in vitro Micro-CT scanning and angiography detection. After 1, 2, 4 and 8 weeks, the femurs of the surgical side were taken for bone histopathologic detection. Results:During the entire experiment, no rats in the control group died while the mortality rate of the rats in the plateau group was as high as 26.7% (8/30). In the plateau group, some organs were pathologically damaged in the rats, fracture union was delayed, and the callus differentiated and matured slowly with the chondrocytes still dominant at the 8th week. The bone mineral density and the maximum load of the femur in the plateau group were significantly lower than those in the control group ( P< 0.05). Angiography showed that the rats in the plateau group had microvascular proliferation which did not penetrate the fracture end at the 8th week. The bone formation indexes like osteocalcin, procollagen type Ⅰ N-terminal propeptide (PⅠNP), and osteoprotegerin of the rats in the plateau group were significantly lower than those in the control group at the 4th week ( P<0.05). The bone resorption indexes like tartrate resistant acid phosphatase 5b (TRACP-5b) and receptor activator for nuclear factor-κB ligand (RANKL) in the plateau group were significantly higher than those in the control group ( P<0.05). Conclusion:A simulated plateau environment at an altitude of 5,000 m may lead to delayed fracture healing in rats.

Effect of chemokines CXCL9 and CXCL10 on bone erosion in patients with rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA.@*METHODS@#In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People's Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman's rank correlation and Logistic regression were used for statistical analysis.@*RESULTS@#The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P < 0.01). Spearman's correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, < 0.001, < 0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P < 0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P < 0.05).@*CONCLUSION@#Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

On the application of blended learning in normal human morphology course / 中华医学教育探索杂志

Objective:To explore the application effect of the blended learning based on Rain Classroom in normal human morphology course.Methods:A total of 118 undergraduates majoring in medical laboratory technology of Batch 2017 and Batch 2018 from Xinjiang Medical University were included in this study, and they were divided into the observation group (Batch 2018) and the control group (Batch 2017), with 59 students in each group, adopting the traditional teaching method and blended learning method based on Rain Classroom respectively. The mid-term, final and comprehensive scores of the two groups were compared by t test and chi-square test through SPSS 23.0. And the evaluation of teaching satisfaction of the observation group was obtained by the questionnaire survey. Results:The mid-term results [(74.02±8.71) vs. (62.00±8.97), t=-6.073, P<0.001], the final results [(83.21±7.73) vs. (70.44±11.43), t=-6.250, P<0.001], and the comprehensive results [(82.26±9.53) vs. (70.52±11.09), t=-6.012, P<0.001] of the observation group were significantly superior than those of the control group ( P<0.05). The excellence rate of the final results (23.72% vs. 3.45%, χ2=10.412, P=0.001) and comprehensive results (18.64% vs. 5.08%, χ2=5.187, P=0.023) in the observation group were significantly higher than those in the control group ( P<0.05). The results of the questionnaire survey showed that the observation group generally had a good satisfaction with the blended learning. Conclusion:The blended learning could make up for the deficiency of the traditional teaching methods, have preferable teaching effects, and get wide recognition from students.

Effect of Crude Epimedii Folium and Processed Epimedii Folium on Kidney Yang Deficiency Edema Model Rats / 中国实验方剂学杂志

Objective: To compare the effects between crude and processed Epimedii Folium on the rats of kidney-Yang deficiency and edema, in order to discuss the mechanism. Method: The rat model of kidney-Yang edema was duplicated with hydrocortisone and doxorubicin hydrochloride. At day 1 and day 8 of modeling, the rats were injected with doxorubicin hydrochloride (3.5 mg·kg-1) via tail vein, while being intraperitoneally injected with hydrocortisone (3.75 mg·kg-1·d-1) for 15 days.After modeling,the rats were divided into model group,crude Epimedii Folium group(204.86 mg·kg-1)and processed Epimedii Folium group(204.86 mg·kg-1), and a normal control group was set up additionally.Rats in each treatment group were given the corresponding drugs,and those in normal and model groups were given the same volume of normal saline by gavage for continuous 14 days.At the end of the administration,24 h urine was measured by rat metabolic cage method; 24 h urinary protein was detected by ultraviolet spectrophotometry; the content of plasma albumin (ALB) and total serum protein (TP) were measured by an automatic biochemical analyzer; and the content of adenosine monophosphate was measured by enzyme-linked immunosorbent assay(ELISA). Cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), triiodothyronine (T3), thyroxine (T4), serum creatinine (SCr), serum urea(BUN), estradiol (E2), testosterone (T) indicator content were determined by enzyme-linked immunosorbent assay(ELISA). Kidney tissues were collected to make pathological section by htoxylin eosin(HE) staining. Result: Compared with the normal group, all the indicators of appearance, biochemistry and pathological section in the model group indicated kidney Yang deficiency edema in the rats (PP2, T indicators to varying degrees(PPP2, T (PPP3, T4 and anal temperature (PPConclusion: Both crude Epimedii Folium group and processed Epimedii Folium group have certain effect in treating kidney Yang deficiency edema, and the possible mechanism is to alleviate glomerular podocyte injury induced by doxorubicin. Their emphasis in the treatment of kidney Yang deficiency edema is different. Crude Epimedii Folium has a cold property, and can treat kidney Yang deficiency edema by strengthening renal excretion function of rats with kidney Yang deficiency edema. Processed Epimedii Folium is processed with sheep oil to produce icariin and other substances, and its property changed from cold to warm, with a focus on alleviating the kidney Yang deficiency status of rats with kidney Yang deficiency edema.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms.@*METHODS@#One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure.@*RESULTS@#The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB.@*CONCLUSION@#Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Effect of electroacupuncture at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on perinatal nicotine-exposure-induced lung function and morphology of neonatal rats / 中国针灸

OBJECTIVE@#To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotineexposureinduced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats.@*METHODS@#A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotineST 36 group (N + ST 36 group) and a nicotineGB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotineexposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture.@*RESULTS@#Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all 0.05).@*CONCLUSION@#Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotineexposureinduced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).

Studies on alkaloids from Ervatamia pandacaqui / 中国中药杂志

To inverstigate the alkaloids from the twigs and leaves of Ervatamia pandacaqui, eleven known alkaloids were isolated by silica gel, Sephadex LH-20, and ODS column chromatography, as well as RP-HPLC. Their structures were elucidated by UV, IR, MS, and NMR spectral data as coronaridine (1), 3-oxocoronaridine (2), 19S-heyneanine (3), 19R-heyneanine (4), voacangine (5), 3-oxovoacangine (6), voacristine (7), 19-epi-voacristine (8), iso-voacangine (9), coronaridine 7-hydroxyindolenine (10), and voacangine 7-hydroxyindolenine (11). Compounds 1-11 were isolated from E. pandacaqui for the first time.

Decomposition Kinetics of Omethoate in Blood / 法医学杂志

Objective To study the decomposition kinetics of omethoate in blood.Methods The acetonitrile precipitated protein was added into the blood, with the chromatographic column of a Waters BEH C18column (2.1 mm×50 mm, 1.7μm), the mobile phase of 5 mmol/L ammonium acetate aqueous solution-methanol, and the gradient elution with a flow rate of 0.3 mL/min and injection volume of 2μL.With electrospray ionization (ESI) source and positive ion detection, qualitative and quantitative analyses were taken using multi-reaction monitoring mode.Omethoate standard was added into blank human blood to the mass concentrations of 0.78, 1.40, 2.30, 4.50, and 7.20μg/mL, and each mass concentration was preserved at 3 temperatures of-20℃, 4℃, and 20℃, respectively.The content of omethoate was detected at different time points (0, 1, 3, 4, 7, 11, 15, 24, 32, 40, 48, 64, 80, 96, and 120 d).Results Different concentrations of omethoate all showed a descended trend in human blood under different temperature conditions.The decomposition in storage environment of-20℃, 4℃, and 20℃was fit to a one-compartment open model with a first-order kinetic process, which could be expressed as Ct=Coe-αt, with the calculated theoretical values of omethoate concentration close to the measured values.Conclusion All concentrations of omethoate are decomposed in the blood, which vary a lot in different preservation conditions.It is suggested that blood samples should be frozen and detected timely in suspected omethoate poisoning cases.

ALEX1 expression in cervical cancer tissues and effect of ALEX1 on cervical cancer cell biology behavior / 中国药理学通报

Aim To investigate ALEX1 gene expres-sion in cervical cancer tissues and adjacent non-can-cerous tissues, and to explore the ALEX1 genetic influ-ence on cell proliferation,cycle and apoptosis of human cervical cancer cell line HeLa. Methods ALEX1 protein expression in cervical cancers and in non-can-cerous cervical tissues was evaluated using immunohis-tochemical method. A small interference RNA targeting ALEX1 gene was transfected into HeLa cells′, and the effect of ALEX1 interference on HeLa cells′ cycle and apoptosis was analysed by flow cytometry. The effect of ALEX1 interference on HeLa cells′ proliferation and sensitivity to resveratrol was analysed by CCK-8 assay. Results ALEX1 protein expression was significantly increased in cervical cancer tissues compared with non-cancerous tissues. HeLa cells′proliferation was inhibi-ted compared with control group and blank group. He-La cells′ sensitivity to resveratrol was enhanced com-pared with control group blank group. Conclution SiRNA silencing of ALEX1 gene could significantly in-hibit HeLa cells′ proliferation and enhance resveratrol ability of inhibiting HeLa cells′proliferation.

Expression of MCP1 gene in serum and tumor tissues in bladder urothelial carcinoma patients and its clinical significance / 肿瘤研究与临床

Objective To investigate the monocyte chemoattractant protein (MCP1) gene expression of the bladder urothelial carcinoma and its correlation with the pathogenesis of the bladder urothelial carcinoma.Methods Thirty cases of patients with the bladder urothelial carcinoma, including 20 cases of male and 10cases of female, were taken the blood and bladder tissue.In control group, 30 cases of non-cancer patients,including 20 cases of male and 10 cases of female, were taken the blood samples.ELISA method was used to detected the concentration of plasma MCP1, immunohistochemical method to investigate the expression of MCP1 in the bladder urothelial carcinoma and adjacent tissues.Real-time quantitative RT-PCR was applied to detected the expression of MCP1. Data of the two groups were comparied and the relationship between the expression of MCP1 and the clinical characteristics of the bladder urothelial carcinoma was analyzed.Results MCP1 in group of patients with the bladder urothelial carcinoma was (193.4±105.7) pg/ml, and higher than that in non-tumor group (91.8±34.6) pg/ml (t = 8.37, P ＜0.001).MCP1 in invasive bladder cancer was (204.3±167.5) pg/ml and superficial bladder cancer was (130.6±69.2) pg/ml (t = 2.667, P = 0.013). By immunohistochemistry, the MCP-1 positive rate in the bladder urothelial carcinoma was 70.0 % (21/30), that in adjacent cancer tissue was 43.3 % (13/30) (χ2 = 4.9, P ＜0.05). The positive rate of MCP1 in invasive bladder cancer in tumor group was 80.0 % (8/10) and that in superficial bladder cancer was 65.0 %(13/20).At the same time, MCP- 1 positive intensity in the bladder urothelial carcinoma was significantly higher than that in adjacent tissues. The intensity in invasive bladder cancer was higher than that in superficial ones. Total RNA and mRNA levels of MCP-1 in the bladder urothelial carcinoma were statistically differences compared with that in adjacent tissues (χ2 = 10.08, P ＜0.05).Conclusion The upregulation of MCP1 gene expression is likely to play an important role in the incidence and metastasis of the bladder urothelial carcinoma.

Time resolved fluoroimmunoassay for Glypican 3 and its preliminary application / 中华核医学杂志

Objective To establish a time resolved fluoroimmunoassay (TRFIA) method for detecting Glypican 3 (GPC3) and to explore the diagnostic value of serum GPC3 for hepatic carcinoma (HCC). Methods Microplate coated with anti-GPC3 monoclonal antibody 7C8 and GP9 labeled with Eu3+ were used to establish TRFIA kit. The serum concentrations of GPC3 in 41 HCC patients and 44 chronic hepatitis (CH) patients were quantitatively analyzed. AFP was detected by with lowest limit of 2.06 μg/L. The CV of inter and intra assay were 12.25% and 12.91%, respectively. The average serum concentration of GPC3 in HCC patients was (86.68±110.39) μg/L (median: 56.98 μg/L). But in CH patients it was only (14.77±29.48) μg/L, which was significantly lower than that in HCC (Wilcoxon W=1335.00, Z=-4.99, P<0.001). With diagnostic cut-off value set at 42.94 μg/L, the diagnostic sensitivity and specificity of TRFIA GPC3 for HCC were 58.5% (24/41) and 95.5%(42/44) respectively. The diagnostic sensitivity of AFP was 46.3% (19/41) in 41 HCC patients, and was raised to 78.0% (32/41) when combined with GPC3. Conclusions Serum GPC3 assay by TRFIA is established and it could increase the diagnostic sensitivity for HCC when combined with AFP.

Diagnosis and treatment of acute focal renal infarction / 中华泌尿外科杂志

Objective To review the clinical diagnosis and treatment of acute focal renal infarction. Methods Three cases of focal renal infarction were reported and the literature was reviewed.The patients aged from 45 to 63 years with mean age of 54. Two cases had low back pain, 1 case with abdominal pain. Based on clinical history, B-ultrasonography and CT scan, focal renal infarction was diagnosed in 3 patients. There were 2 cases on left kidney and 1 case right. All cases were applied digital subtraction angiography (DSA) and thrombolytic anticoagulant therapy. Results Two cases received DSA and thrombolytic therapy. The other one case received pethidine 50 mg, progesterone 20 mg treatment, the salvia infusion and low molecular heparin 6000 U anticoagulant therapy. All patients had symtoms relieved after 1 d. A week later CT scan, 3 cases of renal infarction were apparently disappeared. Serum creatinine and urea nitrogen were normal. Three patients were followed, mean follow-up time was 1. 5 (0. 5-2) years. Conclusions The diagnosis of acute focal renal infarction mainly depends on B-ultrasound and CT. Early diagnosis and treatment is important for achieving recovery of the compromised renal function. Renal infarction should be suspected in the presence of abdominal pain of sudden onset.

Clinical observation of porcelain and composite veneer in repairing dental fluorosis / 中国地方病学杂志

Objective To observe the clinical changes in resin and porcelain veneer in restoring dental fluorosis in order to provide a basis for the repair of dental fluorosis. Methods Fifty six severe dental fluorosis patients were divided into porcelain and resin teeth group in the department of Prosthetics, school of Stomatology, Harbin Medical University during 2005 to 2008. All 162 teeth of 25 patients in porcelain group were veneered with porcelain. 201 teeth of 31 patients in resin group were repaired with resin. To evaluat the clinic effect, the veneer surface color was detected by the Easyshade computer-aided colorimeter when the repair was completed and 18 months afterward. The edge of veneer adaptation, retention, secondary caries and abutment were examined after 18 months, and classified by color, shape, function and feeling. Results The color difference between the porcelain and resin teeth group was 0.27±0.20 and 0.21±0.15 when it was completed, and it was 0.28±0.21 and 0.77± 0.68 respectively after 18 months. The color difference value of the porcelain teeth group was lower when it was completed than 18 months later(t=-13.55, P<0.01). The color difference value of the resin teeth group was lower than the porcelain teeth group after 18 months(t=-12.60, P<0.01). The percentage of level A of veneer adaptation in the porcelain group[100%(162/162)] was higher than the resin group[91.04% (183/201), χ2=15.26, P< 0.01) after 18 months. The clinical effect was divided into three degrees of excellent, moderate or failed, into which the number of the teeth catergorized was 158, 4 and 0 in porcelain group, 148, 56 and 4 in resin group respectively. The clinical effect of the porcelain group was superior to the resin group(χ2=44.24, P<0.01). Conclusions The surface color of porcelain veneer last 16nger than the resin veneer, the adaptation and clinical effect is also superior to the resin veneer. But the long-term efficacy of two methods needs further study, especially of the resin veneer.

Ponder on countermeasures of prevention on endemic fluorosis / 中国地方病学杂志

Enlightened by the essay Affection of Nutrition Factors On Endemic Fluorosis written by professor Li Guang-sheng ,and integrated with the contradictory phenomena in three times epidemic invest igations,the author thought:in epidemic factors of fluorosis,endemic fluorosis not only is related with fluoride intake perday,but also related with nutritional factors,especially calcium in food.The article discussed on countermeasures of prvention of endemic fluorosis in views of the above.