Exploration of construction mode of real-world data system / 中华流行病学杂志

Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.

Studies on the chemical constituents of the anti-osteoporotic part of Lepidium meyenii Walp. produced in Heqing / 药学学报

This study was designed to investigate the chemical constituents of the anti-osteoporotic part of Lepidium meyenii Walp. (maca) produced in Heqing, Yunnan. Seven compounds were isolated from the n-BuOH extract of maca using combination of column chromatographies on MCI resin, silica gel, C18 bonded silica gel, and Sephadex LH-20, followed by semi-preparative HPLC and recrystallization. The purified compounds were identified on the basis of their physicochemical properties and spectral data as macaolidine (1), tryptophan (2), daucosterol (3), (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylicacid (4), chlorogenic acid (5), luteolin (6), and hyperoside (7). Compound 1 is a new phenylacetamide alkaloid, and compounds 4-7 were isolated from Lepidium meyenii for the first time.

Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson's disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China.</p><p><b>METHODS</b>Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Parkinson's Disease Questionnatire-39, Parkinson's Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures.</p><p><b>RESULTS</b>In the "off" state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the "on" state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 μs, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively.</p><p><b>CONCLUSIONS</b>STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control.</p>

Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin II in vascular smooth muscle cell / 生理学报

Angiotensin II (Ang II) and calcitonin gene-related peptide (CGRP) play important roles in vascular injury and protection. In order to determine the role of CGRP receptor component protein (RCP) in signal transduction whereby CGRP and Ang II mediate the expression of vascular peroxidase-1 (VPO1) in vascular smooth muscle cell (VSMC), mouse derived A10 vascular smooth muscle cell line (A10VSMC) was cultured with CGRP or/and Ang II in vitro. RCP-specific small interference RNA (siRNA-RCP) was used to silence oligonucleotide sequence. Western blot and RT-PCR were used to determine the protein and mRNA expressions of RCP and VPO1, respectively. The results showed that the expressions of RCP and VPO1 were increased in the presence of CGRP or Ang II in the quiescent A10VSMC. But the protein expressions of RCP and VPO1 induced by Ang II were decreased by pretreatment of CGRP (P < 0.05). The expressions of VPO1 were decreased in all the groups treated with siRNA-RCP, compared with those of wide-type counterparts. Meanwhile, the expression of VPO1 was significantly induced by CGRP but not Ang II in the siRNA-RCP treated A10VSMCs. Ang II in combination with CGRP increased the protein expression of VPO1 in the siRNA-RCP-transfected cells, compared with Ang II alone, and this effect could be abolished by catalase. The results suggest that RCP may play an important role in the integration of signal transduction whereby CGRP and Ang II receptors jointly regulate VPO1 expression in VSMC.

CD16 expression is an independent prognostic factor for extranodal NK/T cell lymphoma of nasal type / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic features of extranodal NK/T cell lymphoma, nasal type (ENKTCL-N), to explore the expression of NK cell-associated receptors in ENKTCL-N and the relationship with prognosis, and to establish a prognostic model.</p><p><b>METHODS</b>One hundred and twenty-six cases of ENKTCL-N were selected from the files of the Department of Pathology, West China Hospital of Sichuan University. The relevant clinical and follow-up data were collected, and the histopathology was reviewed. All specimens were stained immunohistochemically for CD16, ICAM-1 and LFA-1. RT-PCR was used to detect the expression of CD94, NKG2 and KIR. The relationship between the prognosis of ENKTCL-N, clinical features, histopathological characteristics and expression of these markers were also analyzed.</p><p><b>RESULTS</b>ENKTCL-N mainly occurred in middle-age and young patients (median age, 41 years). The male to female ratio was 3.2:1. Sites more commonly involved were the nose and upper aerodigestive tract whereas those for the non-nasal type were the skin and gut. Only six cases involved two or more extranodal sites. Most (86.5%, 109/126) of the patients were in clinical stages I/II. The tumors showed predominately medium-sized tumor cells and large-sized tumor cells accounted for only 9.5% (12/126). Coagulative necrosis was present in all cases. The expression rates of CD56, CD16, CD94, LFA-1 and ICAM-1 were 82.6% (95/115), 15.1% (19/126), 55.4% (41/74), 40.5% (51/126) and 0, respectively. The expression rate of NKG2 receptor was 90.5% (67/74) overall. NKG2 receptor expression was independent of CD94. The overall expression rate of KIR receptor was 33.8% (25/74) and KIR receptor restriction was not detected in 20.8% (5/24) of the cases. Follow-up data was available in all patients, with median and average survival time being 15 months and 20.2 months, respectively. Survival analysis showed that prognostic factors included the gender, age, disease type, extranodal involvement, stage, the expression of CD16, LFA-1 and CD94. Cox's proportional hazard regression analysis revealed four factors, age, involved site, stage and CD16 expression, were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The age, disease type, stage and CD16 expression are independent prognostic factors. Establishment of a prognostic model based on the above four factors can be more accurate in the prognostication of ENKTCL-N. The differences in the clinical features, prognosis, and expression of NK cell-associated receptors are obvious between nasal NK-cell lymphoma and non-nasal NK-cell lymphoma.</p>

Development and validation of a liquid chromatography-isotope dilution tandem mass spectrometry for determination of olanzapine in human plasma and its application to bioavailability study / 药学学报

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.

Effects of conjugated linoleic acid on expression of GLUT4 protein in skeletal muscle of insulin resistant rat / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the effects of conjugated linoleic acid (CLA) on expression of glucose transporter 4 (GLUT4) protein in skeletal muscle of insulin resistant rat, and explore the mechanism of resisting diabetes by CLA.</p><p><b>METHODS</b>Male Wistar rats were randomly separated into control group, high-fat group and high fat plus CLA group (0.75 g%, 1.50 g%, 3.00 g% by deit weight), and the effects of CLA on blood glucose and insulin levels of insulin resistant rat were observed , by using Western blot technique to measure the expression level of GLUT4 protein in skeletal muscle of insulin resistant rat.</p><p><b>RESULTS</b>The serum insulin and glucose levels of obese rats were (11.11 +/- 2.73) microU/ml, and (5.09 +/- 0.66) mmol/L, the supplement of CLA might decrease the hyperinsulinemia and hyperglycemia, and in CLA groups (0.75 g%, 1.50 g%, 3.00 g% by deit weight) the serum insulin was (6.99 +/- 1.77) microU/ml, (7.36 +/- 1.48) microU/ml and (7.85 +/- 1.60) microU/ml (P < 0.05), and the glucose levels were (4.28 +/- 0.72) mmol/L, (4.18 +/- 0.55) mmol/L (P < 0.05), (4.06 +/- 0.63) mmol/L (P < 0.05) respectively. The expression of GLUT4 protein in skeletal muscle of rat fed with high fat diet were decreased as compared with those fed with basic deit, and CLA might increase the expression of GLUT4 protein in skeletal muscle fed with high fat diet.</p><p><b>CONCLUSIONS</b>CLA improve the insulin resistance of obese rat, possibly acting through increasing the expression of GLUT4 protein in skeletal muscle of rat fed with high fat diet.</p>

Study on the relationship between polymorphisms of susceptible genes in coagulation pathway related to pulmonary thromboembolism in Chinese Han population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the prevalence of beta-fibrinogen gene -455G/A, -148C/T polymorphisms in Chinese Han population and to investigate whether they were associated with pulmonary thromboembolism (PTE).</p><p><b>METHODS</b>The subjects consisted of 101 patients with PTE and 101 healthy controls matched with age and sex, from the same geographic area. All patients were diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography as well as medical history and clinical manifestations. Genome DNA was extracted from whole blood using KI-phenol-chloroform. Genotypes and allele frequencies of fibrinogen beta gene -455G/A, -148C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Restriction enzyme HaeIII and HindIII digestion were used for detecting -455G/A, -148C/T polymorphisms respectively.</p><p><b>RESULTS</b>Regarding fibrinogen beta gene -455G/A and -148C/, the allele frequencies G and A of fibrinogen beta -455 in the controls were 0.931, 0.069 while C and T of -148 were 0.777, 0.223 respectively, which were in good agreement with Hardy-Weinberg equilibrium. There was significant difference of -455G/A genotype frequencies distribution of AA, GA, GG between cases and in controls respectively, but no significant difference was found in the -148C/T polymorphisms. The frequencies of mutation allele -455A were 0.193, 0.169 in cases and in controls with P < 0.05 but there was no statistically significant difference of -148T allele. The presence of A allele of fibrinogen beta -455 was found to be a greater risk factor in cases than in controls. The odds ratio (OR) of GA and GA + AA were 3.723 (1.786 - 7.759), 3.749 (1.842 - 7.630), respectively. When compared with GG genotype, the P value was 0.0001.</p><p><b>CONCLUSION</b>There was a complete linkage disequilibrium between fibrinogen beta -148C/T and -455G/A found. The frequencies of -455A, alleles in PTE disease were apparently higher than that of healthy adults but there was no difference in -148T alleles.</p>

Comparison of unfractionated heparin and low molecular weight heparin in pulmonary thromboembolism: meta-analysis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To pool the data of studies about anticoagulation in non-massive pulmonary thromboembolism (PTE) and evaluate the efficacy and safety of low molecular weight heparin (LMWH) and unfractionated heparin (UFH) as the initial treatment.</p><p><b>METHODS</b>MEDLINE CD-ROM from January 1966 to August 2003 and CBM CD-ROM from January 1978 to August 2003 were chosen for searching the randomized clinical trials (RCTs) that compared the efficacy or safety of LMWH and UFH in non-massive PTE. A meta-analysis was employed to evaluate the results of these two therapies.</p><p><b>RESULTS</b>Five RCTs including 999 cases were analyzed. Compared with UFH, the combined odds ratio (OR) of LMWH in treating PTE was as follows: (1) The total OR of mortality of PTE patients treated with LMWH was 0.81 (95%CI 0.36-1.81, P > 0.05); (2) The total OR of recurrence of venous thromboembolism (VTE) in PTE patients treated with LMWH was 0.37 (95%CI 0.14-1.00, P=0.05); (3) The total OR of bleeding in LMWH was 0.47 (95%CI 0.16-1.39, P > 0.05);(4) The total OR of heparin-induced thrombocytopenia (HIT) in LMWH was 0.66 (95%CI 0.06-6.92, P > 0.05).</p><p><b>CONCLUSIONS</b>LMWH and UFH can reduce the mortality and recurrence of VTE in patients with PTE in the same degree. The risk of major bleeding was similar in the two treatment groups. Initial subcutaneous therapy with the LMWH appeared to be as effective and safe as intravenous UFH in the initial treatment of PTE.</p>