Research advances on dihydrofolate reductase inhibitors in the treatment of tumors and bacterial infections / 药学学报

Dihydrofolate reductase (DHFR) is a well-known key target in the treatment of tumors, bacterial infections, and parasitic infections; and it plays a critical role in the biosynthesis of cellular DNA. DHFR inhibitors interfere with one-carbon metabolism by inhibiting substrate binding to DHFR, thereby inhibiting cell proliferation. Research on DHFR inhibitors has continued since the 1940s. To date, a variety of DHFR inhibitors have come into the market, primarily used for anti-tumor, antibacterial, antiparasitic, and anti-inflammatory therapy. This review summarizes the research progress of DHFR inhibitors with antitumor or antibacterial effects in recent years based on the classification of single-target and dual-target and looks forward to the opportunities and challenges faced by the work in this field.

Scutellarin alleviates lipopolysaccharide-induced renal injury via mediating cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 expression to inhibit nuclear factor-κB signaling pathway / 中华危重病急救医学

Objective:To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI).Methods:① In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). ② In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 μmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. Results:① The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. ② The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2 -ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2 -ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1β mRNA (2 -ΔΔCT) : 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2 -ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2 -ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1β mRNA (2 -ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2 -ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2 -ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. Conclusions:Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway / 中国中药杂志

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Naringenin protects ischemia-reperfusion-induced acute kidney injury by nuclear factor κB / 中华肾脏病杂志

Objective:To explore the effect and involved mechanism of naringenin on acute kidney injury (AKI) induced by ischemia-reperfusion (IR).Methods:The IR-AKI rat model was constructed using the classic bilateral renal pedicle clamping method, then renal function and pathological change were assessed, as well as inflammation-associated genes were detected by quantitative real-time PCR. The hub genes were selected through differential gene analysis and protein-protein interaction network analysis, and their transcription factors were predicted, which constructed a protein library together. The proteins binding to naringenin were selected by reverse molecular docking analysis and further their binding patterns were predicted to explore the mechanism of naringenin. Finally, the results of bioinformatics were verified by experimental methods.Results:Compared with the AKI group, the kidney pathology of the rats in the naringenin pretreatment group was significantly improved, and the renal tubular injury score was reduced ( P<0.01); meanwhile the serum creatinine level and the mRNA expression of the kidney injury molecule 1 (KIM-1) were significantly decreased (both P<0.05). Compared to sham group, IR-AKI increased the level of nuclear factor κB (NF-κB), tumor necrosis factor-α and interleukin-1β (all P<0.05), which reversed by naringenin indicated that naringenin inhibited inflammation in IR-AKI. Differential gene analysis was performed on the GSE98622 data set, and 359 differential genes were obtained. In reverse molecular docking, the proteins with smallest binding energy including NFKBIA, BCL3, NFKB2 and RELA were considered to be related to the preventive effect of naringenin, which were mainly enriched in NF-κB-related inflammation pathways. Domain functional analysis of NF-κB-related genes showed that naringenin could stably bind to its key domain. According to quantitative real-time PCR results, naringenin increased BCL3 level after AKI ( P<0.05), and further decreased the expression level of RELA and NFKB2 (both P<0.05). Conclusion:Naringenin protects IR-AKI by alleviating inflammation, and its mechanism is related to increasing BCL3 and thereby inhibiting the NF-κB pathway.

Comparison of Detoxification Effect of Different Solvent Extracts of Lysimachiae Herba on Toxicity Induced by Tripterygii Radix et Rhizoma / 中国实验方剂学杂志

Objective:To investigate the effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma. Method:Ninety male SPF Kunming mice were randomly divided into 9 groups according to their body weight，control group， Lysimachiae Herba water extract group， Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2，1 g·kg^-1 based on crude drugs， respectively. The control group was given an equal volume of solvent， and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay （ELISA） was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile， principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma. Result:Compared with control group， Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase（ALT），aspartic acid amino transferase（AST），alkaline phosphatase（ALP） in serum of mice， and the levels of malondialdehyde （MDA） in liver， and comprehensive score of toxicity （Z value） produced by the above four indexes increased significantly （<italic>P</italic><0.01）. The levels of total superoxide dismutase （T-SOD），glutathione-peroxidase （GPX），glutathione-S transferase （GST） decreased significantly （<italic>P</italic><0.01） in liver. Compared with Tripterygii Radix et Rhizoma group， after intervention with extracts of two solvents （water， 30% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP and liver MDA were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the levels of liver T-SOD， GPX and GST were significantly increased （<italic>P</italic><0.01）. After intervention with extracts of two solvents （60% ethanol， 95% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP were significantly decreased （<italic>P</italic><0.01）， and liver GPX levels were significantly increased （<italic>P</italic><0.01）. After the intervention with ethyl acetate extract of Lysimachiae Herba， only the level of serum AST was significantly decreased （<italic>P</italic><0.05） and the level of GPX was significantly increased （<italic>P</italic><0.05）. After the intervention with extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol， ethyl acetate） of Lysimachiae Herba， it can significantly reduce the comprehensive score of toxicity （<italic>P</italic><0.01）. The overall decline rates of toxicity were 127.5%， 113.4%， 98.1%， 56.3% and 31.0% respectively. Among them， the toxicity reduction rate of the extracts with water as a solvent was 14.1%， 29.4%， 71.2%， 96.5% higher than those of other solvent extracts with ethanol. Conclusion:The extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol and ethyl acetate） of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them， water and 30% ethanol are the best solvents for detoxification， especially water as the extraction solvent， and with the increase of ethanol content or fat solubility of extraction solvent， the detoxification shows a downward trend.

Processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae decoction / 中国中药杂志

On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 μg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".

Risk factors of acute kidney injury in hospitalized patients with infective endocarditis and their predictive values / 中华危重病急救医学

Objective:To analyze the risk factors of acute kidney injury (AKI) in hospitalized patients with infective endocarditis (IE), construct prediction model, and discuss its predictive value.Methods:The clinical data of 402 adult inpatients diagnosed with IE admitted to the Affiliated Hospital of Qingdao University from January 2010 to January 2020 were retrospectively analyzed. The patients were divided into the AKI group and the non-AKI group. The clinical data, such as gender, age, presence of diabetes, basic estimated glomerular filtration rate (eGFR), laboratory indexes at admission, involvement of valves, presence of sepsis, medication during hospitalization, surgery and outcome of the two groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of AKI in IE inpatients. A predictive model was constructed, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model.Results:A total of 290 patients with IE were enrolled, including 198 non-AKI patients and 92 AKI patients. The incidence of AKI was 31.7%. Among the 92 AKI patients, 46 patients were at AKI stage 1 (50.0%), while 46 patients were at AKI stage 2 and stage 3 (50.0%). Compared with the non-AKI group, patients in the AKI group were older [years old: 64 (55, 71) vs. 55 (46, 63)], and had lower basic eGFR (mL·min -1·1.73 m -2: 64.6±13.6 vs. 82.9±19.5), higher proportion of diabetic and incidence of sepsis (16.3% vs. 8.6%, 38.0% vs. 13.1%), more frequent use of angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists (ACEI/ARB), diuretics and non-steroidal anti-inflammatory drugs (NSAIDs; 25.0% vs. 15.2%, 82.6% vs. 63.1%, 58.7% vs. 24.2%), more abnormal urine test results (hematuria or proteinuria, 35.9% vs. 22.7%), higher pathogen culture negative rate (73.9% vs. 51.5%), lower Gram positive (G +) cocci infection rate and surgery rate (22.8% vs. 40.4%, 60.9% vs. 81.8 %), with significant differences (all P < 0.05). There were no significant differences in the gender, number and location of involved valves, and laboratory indexes at admission between the two groups. Compared with the non-AKI group, the inpatient mortality rate of the AKI group was higher (30.4% vs. 8.6%, P < 0.01), and the inpatient mortality rate of patients with AKI stage 2 and stage 3 was significantly higher than that of patients with AKI stage 1 (43.5% vs. 17.4%, P < 0.01). In multivariate Logistic regression analysis, the lower basic eGFR [hazard ratio ( HR) = 0.136, 95% confidence interval (95% CI) was 0.066-0.280], sepsis ( HR = 6.100, 95% CI was 2.394-15.543), demand for NSAIDs ( HR = 2.990, 95% CI was 1.184-7.546) and radiocontrast agent ( HR = 3.153, 95% CI was 1.207-8.238) were independent risk factors for AKI in hospitalized patients with IE (all P < 0.05). A prediction model was constructed based on the above risk factors, and ROC curve analysis showed that the area under the ROC curve (AUC) of prediction model for AKI was 0.888 (95% CI was 0.833-0.943, P < 0.01) with sensitivity of 86.4% and specificity of 80.9%. Conclusions:In the IE-susceptible population, low basic eGFR, sepsis, the need for NSAIDs and contrast agent are independent risk factors to AKI. The predictive model constructed by the above risk factors has certain predictive value for the occurrence of AKI in the IE inpatients.

Preoperative evaluation of acute renal injury after hepatectomy / 中华肾脏病杂志

Objective To explore the risk factors of post-hepatectomy acute kidney injury (AKI),a Nomogram predictive model of secondary AKI after hepatectomy was established which can provide guidance for the selection of clinically relevant treatment plans and improve the prognosis of surgical patients.Methods A total of 2769 patients who underwent hepatectomy in the Affiliated Hospital of Qingdao University from October 2012 to July 2018 were included in the study.The post-hepatectomy AKI was diagnosed according to the KDIGO AKI criteria in 2012.The selected patients were divided into AKI group (n=133) and non-AKI group (n=2636);they were divided into training group (n=2050) and test group (n=719) according to Enrollment time.The differences of preoperative clinical data,length of hospital stay,and in-hospital mortality between patients with AKI and non-AKI group were compared.The risk factors of post-hepatectomy AKI were evaluated by the Cox regression.A Nomogram predictive model of AKI after hepatectomy was established,and receiver operating curve (ROC) and consistency curve were used to verify the accuracy of the predictive model.Results The incidence of AKI after hepatectomy was 4.80％(133/2769).Compared with non-AKI group,preoperative serum albumin,hemoglobin,and hematocrit levels were lower in AKI group;the level of blood transaminase,total bilirubin,alkaline phosphatase,triglyceride,lactate dehydrogenase,and fibrinogen were higher (P ＜ 0.050);the proportion of preoperative aspirin application was higher (P ＜ 0.001);the duration of operation was longer (P=0.002);the proportion of open surgery was higher (P ＜ 0.001);the mortality rate was higher (P ＜ 0.050);the length of hospital stay was longer (P ＜ 0.050).Cox regression results showed hypertriglyceridemia,hypoalbuminemia,alkaline phosphatase,aspartate aminotransferase,open surgery,lower preoperative glomerular filtration rate,aspirin and duration of surgery were independent risk factors for AKI.We incorporated these indicators into the Nomogram to establish a predictive model for AKI after hepatectomy,the area under ROC curve was 0.764.The area under ROC curve of the test group was 0.781.Conclusion The Nomogram predicting model of AKI after hepatectomy has high accuracy,which is helpful for prognosis of patients who underwent hepatectomy.

Reviews on natural naphthoquinones and their bioactivities / 中国中药杂志

The naphthaquinones are widely distributed in plants. They are usually in higher plants, but a few of them were also found in microorganisms. There is a lot of research showing that they had multiple pharmaco-activities such as cytotoxic, antioxidant, anti-inflammatory and antibacterial activities, etc. In recent years, they have attracted extensive attention at home and abroad especially in terms of the anti-tumor activity. For further research, 69 new natural naphthoquinones reported in the last five years (2013-2017) were reviewed. They were divided into five major types: simple 1,4-naphthoquinones, furan and pyran naphthoquinones, 1,2-naphthoquinones, naphthohydroquinones and naphthoquinone polymers, which showed cytotoxic, antioxidative, anti-inflammatory and antibacterial biological activities, et al. The research of these compounds in the future was also proposed.

A cohort study on mortality and risk of death among population diagnosis as dementia, at base-line survey, in Beijing / 中华流行病学杂志

Objective To study the mortality and risk of death on dementia among ageing population.Methods A random sample including 2788 elderly residents was studied.Dementia was diagnosed under the two-phase procedure in 1997.In phase 1,questionnaire was administered,including the Mini-Mental State Examination (MMSE) tested.In phase 2,all the elderly who showed low MMSE score and some with normal MMSE score,were examined by neurologists.The clinical diagnosis of dementia was set up by two neurologists according to the criteria of DSM- Ⅲ -R and NINCDS-ADRDA.The same sample was followed up in 2000 and 2004 the same way and data on deaths and causes was gathered.The overall time for follow-up was 7.25 years.Results 171 cases with dementia were diagnosed from 2788 subjects in 1997,with a crude death rate(CDR) of dementia was 7.8 per 1000 person-years and age-standardized CDR as 5.5 per 1000 person-years.The death rate was increased exponentially with age.In the dementia group,the total number of deaths was 133,with the CDR as 236 per 1000 person-years and the age-standardized CDR as 206 per 1000 person-years,in the end of the survey.In the non-dementia group,the total number of deaths was 680,with CDR as 40 per 1000 person-years and the age-standardized CDR as 31 per 1000 person-years.The difference in the two groups was statistically significant.The hazard ratio (HR) of dementia death appeared to be the biggest in the 60-74-year group than the other groups.Data was analyzed with the Cox proportional hazards model after making necessary adjustment on potential covariates with the HR of dementia as 2.181 (95％CI:1.751-2.717).The HRs were 2.524 (95％CI:1.964-3.243) in Alzheimer's disease and 1.859 (95％ CI:1.213-2.850) in vascular dementia.Conclusion The CDR and HR of dementia were higher than the non-dementia group in the aging population,showing that dementia was one of the most important risk factors on death in the aging population.

Study on the incidence and risk factors of dementia in elderly residents from communities in Beijing / 中华流行病学杂志

Objective To study the incidence of dementia and its risk factors among the elderly living in the community of Beijing. Methods A sample of 2788 elderly residents from Beijing were investigated regarding the incidence of dementia which was diagnosed using two-stage method in 1997. In the first stage, questionnaire was filled, including MMSE checked up. In the second stage, all the elderly who had lower MMSE score and some with normal MMSE score were examined by neurologists. The clinical diagnosis of dementia was set up by two neurologists according to the criteria of DSM- Ⅲ -R and NINCDS-ADRDA. The same sample was followed up on 2000 and 2004 by the same way, with the overall time for following-up as 7.25 years. Results 171dementias cases were diagnosed among the 2788 elderly in 1997. At the end of the survey, another 180 new cases developed. The average weighted incidence was 0.84/100 person year, adjusted by age (it's same followed), with 0.64/100 person year in males and 1.01/100 person years in females. The incidence of vascular dementia was 0.35/100 person years, with male as 0.39/100 person year and female as 0.32/100 person years. The incidence of dementia was increasing with age, but decreasing with time of education by Multinomial Logistic Regression Analysis. Old age and illiterate appeared to be the risk factors for dementia. People with stroke history and elevated systolic blood pressure were risk factors for vascular dementia. Conclusion The incidence of dementia in the elderly in Beijing was higher than in other areas of China. Old age and illiterate were risk factors for dementia. Being male, illiterate, with stroke history and elevated systolic blood pressure were risk factors for vascular dementia.

Study on the relationship between somatic health and incidence of depression in the elderly / 中华流行病学杂志

<p><b>OBJECTIVE</b>In order to explore the risk factors of geriatric depression, a longitudinal follow-up study was conducted on elderly population living in the community so as to provide evidence for the development of depression prevention and control.</p><p><b>METHODS</b>A sampled population consisting 2506 elderly was selected from urban and rural communities in Beijing, using well-established sampling techniques as cluster, stratification and random selection. Data was collected by trained staff members, using standard survey instruments in 2000 and 2004.</p><p><b>RESULTS</b>Longitudinal study showed that the four-year cumulative incidence of the geriatric depression in Beijing was 10.58%. Difference on were evident intelligence/education, with the rates for illiteracy (15.2%) and primary school (10.5%) significantly higher than that of junior high school and above (5.1%) (chi2 = 26.587, P = 0.000). Rates also varied substantially with place of residence, individuals living in rural areas had a substantially higher rate of depression (15.4%) than those individuals dwelling in urban district (6.1%) (chi2 = 31.163, P = 0.000). Poor self-rated health condition (chi2 = 23.385, P = 0.000), cognitive impairment (chi2 = 11.947, P = 0.001) and limitations in physical functioning (ADL: chi2 = 15.930, P = 0.000; IADL: chi2 = 9.501, P = 0.002) were related to the worsening of depressive symptoms. Results from logistic regression analysis indicated that education level, dwelling area, self-rated health condition and ADL were the independent risk factors.</p><p><b>CONCLUSION</b>Lower educational level, dwelling situation, poor self-rated health condition as well as ADL damage might increase the incidence of depression, suggesting more attention needs to be paid to improve somatic function of elderly in order to decrease the incidence of geriatric depression and to improve the prognosis of the disease and the quality of life.</p>

Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded guar sulfate / 生物医学工程学杂志

Degraded guar was prepared by acid with guar as the main material, which was then brought into reaction with chlorosulfonic acid under proper conditions, the sulfonated degraded guar was obtained successfully. The effects of sulfonation conditions on the SO4(2-) content were investigated, and the proper reaction conditions were determined. The results of infrared spectrometry showed that this sulfated derivative is a novel heparin-like polysaccharide. At the same time, the selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded guar gum sulfate was studied. The experimental results showed that degraded guar gum sulfate is a novel LDL/ Fib purifying agent. When pH= 5.15 and the initial concentration of the degraded guar gum sulfate is 2500 mg/L, the reduction percentages were about 60%-66% for total cholesterol, about 76%-89% for LDL and very low-density lipoproteins (VLDL), and almost 100% for fibrinogen. There were no significant changes regarding the level of high-density lipoproteins and total proteins.

Study on the isolated systolic hypertension and its prognosis among 2866 elderly residents at the community level in Beijing / 中华流行病学杂志

<p><b>OBJECTIVE</b>We followed a group of community residents above 60 years old to investigate how isolated systolic hypertension (ISH) could influence the prognosis in the long run among the elderly.</p><p><b>METHODS</b>A selected sample of 60 year olds and over from the Beijing residential communities was randomized ascertained to a longitudinal study. Baseline data was collected in 1993 and 11 years later in 2004, the all-cause death, mortality of cardiovascular and cerebrovascular diseases were observed and analyzed.</p><p><b>RESULTS</b>(1) The morbidity of hypertension(HT) was 61.7% and ISH was 27.8% seen in baseline survey while the SBP was increasing with age. (2) The longitudinal study showed that the total mortality and the mortality of cardiovascular and cerebrovascular diseases in HT group were higher than in the normal blood pressure(BP) group. The total mortality in the group ISH was higher than in normal BP group (55.2%: 46.2%; P < 0.01). The mortality OR for group ISH/group normal BP was 1.4 and group DSH/group normal BP was 1.6. The level of SBP was related to prognosis too which showed that the mortality appeared the lowest in 120-139 mm Hg group, and increased when the level of SBP was above 140 mm Hg.</p><p><b>CONCLUSION</b>SBP was an independent risk factor on the all-cause mortality and the mortality of cerebrovascular diseases in eldevly. ISH also appeared a risk factor on the prognosis among the elderly, suggesting that more attention should be paid to it and treatment be carefully addressed.</p>

Effect of Hypertension on Life Quality in Elderly / 中华高血压杂志

Objective To explore the effect of hypertension on the life quality in elderly.Methods A cohort of 1847 elderly in community in Beijing was recruited.Blood pressur,body structural and mental heath,cognition, activity and life satisfaction were evaluated by physical examination,CES-D scale,MMSE,and ADL,IADL scale.Results The life quality of the elderly hypertension was worse than those of normotensive;the morbidi- ties of chronic disease related to hypertension were higher and the cognitive ability worse with the duration of hy- pertension.The prevalence of depression was higher and the vitality was decreased as the rising of blood pres- sure.Conclusion Prevention and control hypertension improve life quality in elderly hypertension.

Study on Depression of Hypertension and Associated Factors in Elderly Population in the Community of Beijing / 中华高血压杂志

Objective To explore the depression status of hypertension and analyze the associated factors in the elderly population in a community of Beijing.Methods This cohort of 1064 elderly people in the community were screened with Centerfor Epidemiology Scale(CES-D). Results Those who lived in rural(21.6% vs city 7.3%),illiterate(19.9% vs literate 11.2%),mateless(19.7% vs mate 12.4%),lower income(21.9% vs high in- come 9.8%),life accidents(23.2% vs without life accidents 8.6%),sleep disorder(31.0% vs sleep good 8.7%) and lower living abilities(26.7% vs high living ability 9.0%)had higher incidence of depression(all P

Standardized skill of mastoscopic axillary lymph node dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the standardized skill of mastoscopic axillary lymph node dissection (MALND).</p><p><b>METHODS</b>The clinical results and operation experiences of 473 mastoscopic lymph node dissections performed were analyzed.</p><p><b>RESULT</b>The operation time was 22 - 156 minutes with the average of 42. The operative bleeding was minimal. No case was converted to conventionally open operation because of the uncontrolled bleeding. Fourteen (4 - 38) lymph nodes were removed. There was no intra- or post-operative complication.</p><p><b>CONCLUSION</b>The special view of mastoscopic lymph node dissection makes operative dissection clear. The suitable procedure and standardization of the operative method can stride over the learning curve, so as to quicken the operation and avoid the operative complication.</p>

Effect of fractalkine on neuroprotection / 中国病理生理杂志

The chemokine fractalkine primarily involves in chemotaxis,adherence and inflammation.Recently it has been discovered owning the ability of inhibiting cell death in neurons and glial cells,as well as protecting central nervous system from toxic damage.Fractalkine reduces the toxicity to neurons and glial cells mediated by excessive Fas L,glutamate(Glu) or lipopolysaccharide(LPS).In vivo neutralization of endogenous brain fractalkine signal pathway increases inflammatory cytokines secretion and neuronal cell death induced by LPS.Fractalkine may achieve its neuroprotective property through influencing expression of pro-apoptotic and anti-apoptotic proteins,intracellular Ca2+ level and inflammatory cytokines secretion via protein kinase B(PKB)/Akt and extracellular signal-regulated kinase(ERK)/MAPK pathways.