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Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them.

Background To establish and validate a high-resolution magnetic resonance imaging (HRMRI)-based radiomic nomogram for prediction of preoperative perineural invasion (PNI) of rectal cancer (RC). Methods Our retrospective study included 140 subjects with RC (99 in the training cohort and 41 in the validation cohort) who underwent a preoperative HRMRI scan between December 2016 and December 2019. All subjects underwent radical surgery, and then PNI status was evaluated by a qualified pathologist. A total of 396 radiomic features were extracted from oblique axial T2 weighted images, and optimal features were selected to construct a radiomic signature. A combined nomogram was established by incorporating the radiomic signature, HRMRI findings, and clinical risk factors selected by using multivariable logistic regression. Results The predictive nomogram of PNI included a radiomic signature, and MRI-reported tumor stage (mT-stage). Clinical risk factors failed to increase the predictive value. Favorable discrimination was achieved between PNI-positive and PNI-negative groups using the radiomic nomogram. The area under the curve (AUC) was 0.81 (95% confidence interval [CI], 0.71–0.91) in the training cohort and 0.75 (95% CI, 0.58–0.92) in the validation cohort. Moreover, our result highlighted that the radiomic nomogram was clinically beneficial, as evidenced by a decision curve analysis. Conclusions HRMRI-based radiomic nomogram could be helpful in the prediction of preoperative PNI in RC patients.

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

Thyroid cancer (TC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide. The incidence of TC, especially that of papillary thyroid carcinoma (PTC); has increased rapidly in recent decades. Autoimmune thyroid disease (AITD) is closely related to TC and has an estimated prevalence of 5%. Thus, it is becoming increasingly important to identify potential diagnostic biomarkers and therapeutic targets for TC and AITD. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently bonded circular structures that lack 5'-3' polarity and polyadenylated tails. Several circRNAs play crucial roles in the development of various diseases, including TC and AITD, and could be important new biomarkers and/or targets for the diagnosis and therapy of such disorders. Although there are four subtypes of TC, research on circRNA has largely focused on its connection to PTC. Therefore, this review mainly summarizes the relationships between circRNAs and PTC and AITD, including the molecular mechanisms underlying these relationships. In particular, the functions of "miRNA sponges" and their interactions with proteins and RNA are discussed. The possible targeting of circRNAs for the prevention, diagnosis, and treatment of TC and AITD is also described. CircRNAs could be potential biomarkers of TC and AITD, although validation will be required before they can be implemented in clinical practice.

Background Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase‐activating protein (GAP) and modulate integrin‐mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

Epidemiological and animal studies indicate that increased exposure to bisphenol A (BPA) induces various human cardiovascular diseases (CVDs), including myocardial infarction, arrhythmias, dilated cardiomyopathy, atherosclerosis, and hypertension. Bisphenol S (BPS), an alternative to BPA, is increasingly present in various consumer products and human bodies worldwide. Recently, emerging evidence has shown that BPS might be related to cardiovascular disorders. In this review, we present striking evidence of the correlation between BPA exposure and various CVDs, and show that a nonmonotonic dose-response curve (NMDRC) was common in studies of the CV effects of BPA in vivo. The CV impairment induced by low doses of BPA should be highlighted, especially during developmental exposure or during coexposure with other risk factors. Furthermore, we explored the possible underlying mechanisms of these effects-particularly nuclear receptor signaling, ion channels, and epigenetic mechanisms-and the possible participation of lipid metabolism, oxidative stress and cell signaling. As the potential risks of BPA exposure in humans are still noteworthy, studies of BPA in CVDs should be strengthened, especially with respect to the mechanisms, prevention and treatment. Moreover, the potential CV risk of BPS reported by in vivo studies calls for immediate epidemiological investigations and animal studies to reveal the relationships of BPS and other BPA alternatives with human CVDs.

Background: To study the cost-efficacy of docetaxel and pemetrexed as single agents versus platinum-based combination agents in second-line treatment of stage IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating chemotherapeutic indexes and medical costs. Methods: Treatment responses were evaluated by progression-free survival (PFS), overall survival (OS), hematological and gastrointestinal toxicities. Results: Two hundred and seven stage IIIb or IV NSCLC patients were recruited to this clinical observation retrospective study. Thirty-four subjects were treated with docetaxel (group A), 98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with pemetrexed (group C), and 33 patients with platinum-based doublet combination therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and 4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and 4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88, 13.17, 12.40 and 13.04 months, respectively, without significant differences. The total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and 15,291, respectively. Conclusions: Platinum-based doublet chemotherapy with docetaxel or pemetrexed could significantly increase PFS, however, without significant OS improvement in comparison with using them as single agents. The medical expenses associated with doublet therapy were much higher than those associated with single therapy with a significant portion of the medical expenses spent on treating hematological and gastrointestinal toxicity.

Mecobalamin, one of the coenzyme forms of vitamin B(12), acts as an important cofactor in the activities of B(12)-dependent methyltransferases. Since the discovery of mecobalamin, it has been applied mainly in the treatment of hyperhomocysteinaemia and peripheral neuropathy. However, there is still lack of a systemic review on the clinical administration of mecobalamin and its potential mechanism.To review the mechanism, clinical efficacy and safety of mecobalamin in the treatment of hyperhomocysteinaemia and peripheral neuropathy.First, the potential mechanism, pharmacokinetics and metabolism of mecobalamin were clarified. In addition, the clinical administration including efficacy, safety and tolerability of mecobalamin as monotherapy or combined therapy in the treatment of hyperhomocysteinaemia and peripheral neuropathy were also detailed.Although both monotherapy and combined therapy can lower plasma/serum homocysteine levels and improve the neuropathic symptoms, combined therapy with other B vitamins seems to be more effective. However, more precise, double-blind and randomised control studies are necessary to confirm the efficacy of mecobalamin on hyperhomocysteinaemia, peripheral neuropathy interaction, and cardiovascular, neurological and osteoporotic mortality or morbidity.

To identify Streptococcus mutans (S. mutans) in carious patients' saliva using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to establish a faster and more accurate method to identify S. mutans.In this study, a total of 90 carious patients from Department of Endodontics of Peking University School of Stomatology were recruited. All these patients' saliva was collected. After extracting the protein of the samples, they were identified by MALDI-TOF MS. The composite profile was analyzed using BioExplorer 1.0 software. The scores ≥ 25 were considered as S. mutans, whereas the scores25 were as considered as non S. mutans. Finally, these results were compared with 16S rDNA sequencing to figure out the sensitivity and concordance rate, respectively.The sensitivity of MALDI-TOF MS was 96.0%, and the concordance rate compared with 16S rDNA sequencing was as high as 98.7%.MALDI-TOF MS is high throughput, rapid and easy to perform in comparison to other conventional methods. It has a high sensivity and concordance rate. Thus, MALDI-TOF MS can serve as an effective tool for identification of S. mutans.

To access the prevalence of menopause-like symptoms, and their related factors in old and middle-aged males in the area of Hefei.This study included 1 026 males aged over 45 years that came to the clinic for health examination. We collected their personal data, and evaluated their general health status and the results of the questionnaire investigation using the Aging Males' Symptoms (AMS) scale.The total incidence of menopause-like symptoms was 64.7% among the old and middle-aged males in Hefei area, of which 58.1% were mild, 30.9% moderate and 11.0% severe. The average AMS score was 31.2 +/- 6.8, in which the scores on psychological, physical and sexual function symptoms were 8.3 +/- 2.1, 12.4 +/- 4.8 and 9.3 +/- 4.5, respectively. Sexual function symptoms were increased significantly with the increase of age (P0.05), but psychological and physical symptoms showed no obvious correlation with age (P0.05). The main risk factors of menopause-like symptoms included age, smoking, diabetes, cardiovascular diseases, and obesity, but physical exercise was an important protective factor against them.With the increase of age, the prevalence of male menopause-like symptoms rises and sexual function declines gradually, but psychological and physical scores are not affected significantly. Age, general health status and lifestyle are closely associated with the prevalence of menopause-like symptoms among old and middle-aged males.

The aim of this study was to evaluate the safety and effectiveness of fast-track surgery combined with laparoscopy-assisted radical distal gastrectomy for gastric cancer.Eighty-eight eligible patients were randomly assigned into four groups: (1) fast-track surgery (FTS) + laparoscopy-assisted radical distal gastrectomy (LADG), treated with LADG and FTS treatment; (2) LADG, treated with LADG and traditional treatment; (3) FTS + open distal grastectomy (ODG), treated with ODG and FTS treatment; and (4) ODG, treated with ODG and traditional treatment. The clinical parameters and serum indicators were compared.Compared with the ODG group, the other three groups had earlier first flatus and shorter postoperative hospital stay (all P 0.01; all P 0.05), especially in the FTS + LADG group. The level of ALB was higher in the FTS + LADG group than in the LADG group at 4 and 7 days after surgery (P 0.05, P 0.01). The level of CRP in the FTS + LADG group was lower than in the FTS+ODG group at 4 and 7 days after surgery (P 0.05, P 0.05). The FTS + ODG group had lowest medical costs.Combination of FTS and LADG in gastric cancer is safe, feasible, and efficient and can improve nutritional status, lessen postoperative stress, and accelerate postoperative rehabilitation. Compared with FTS + ODG and LADG, its advantages were limited in short-term follow-up.

Pemetrexed is a novel folic acid antagonist with multiple targets, which has been widely used in the treatment of non-small cell lung cancer (NSCLC). The objective of this study was to compare the effects and toxicities in NSCLC patients treated with pemetrexed monotherapy versus pemetrexed plus a platinum combination agent, so as to provide a basis for standard second-line chemotherapy.The clinical data of 52 patients with NSCLC who were admitted to Shanghai Chest Hospital from August 2006 to October 2008 were retrospectively analyzed. Ten of the 52 patients received pemetrexed monotherapy, and the other 42 patients received the pemetrexed plus platinum regimen. The primary end point was overall survival (OS). The progression-free survival time (PFS) was analyzed and the effects and toxicities were assessed. Survival analysis was evaluated by Kaplan-Meier method. Single factor analysis and the COX regression model were done to analyze the relationship between the influential factors and the prognosis of disease. The elderly patients (or = 60 years old) were analyzed separately as a subgroup.No statistically significant increase in OS (chi(2) = 0.09, P = 0.76), PFS (chi(2) = 0.15, P = 0.70), disease control rate (DCR) (chi(2) = 0.06, P = 0.81) or 1-year survival rate (chi(2) = 0.33, P = 0.57) was found between the two regimens. Single factor analysis showed that the factors including surgery history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC (all P0.05). COX regression analysis demonstrated that surgery history (P = 0.041) and performance status (PS) score before treatment (P = 0.043) may be associated with survival. The toxicity of the two regimens was similar. In the subgroup of elderly patients, no significant difference in OS (chi(2) = 0.01, P = 0.94), PFS (chi(2) = 0.14, P = 0.70), DCR (chi(2) = 0.004, P = 0.95), or 1-year survival rate (chi(2) = 0.03, P = 0.87) was found between the two regimens. The toxicity of combination therapy was significantly higher in terms of hematologic (chi(2) = 9.95, P = 0.01) and gastrointestinal adverse events (chi(2) = 7.66, P = 0.03).There is no significant difference in survival or side effects between these two regimens. For elderly patients (or = 60), pemetrexed monotherapy shows similar efficacy and a better safety profile when compared with pemetrexed combination therapy.

To compare the therapeutic efficacies and toxicities of single-agent docetaxel or docetaxel plus platinum combination agent in patients with advanced non-small cell lung cancer (NSCLC) so as to provide rationales for standard second-line chemotherapy.The clinical data from 152 patients with NSCLC who were admitted into Chest Hospital Affiliated to Shanghai Jiaotong University, from January 2004 to May 2008 were retrospectively analyzed. Forty patients were treated with single-agent docetaxel (single-agent group, 16 and 24 patients with stages IIIb and IV disease respectively; 32 patients with PS score 0-1 before treatment and 8 patients with PS score 2 before treatment), and 112 patients were treated with docetaxel plus platinum combination agent (combination group, 29 and 83 patients with stage IIIb and IV disease respectively; 98 patients with PS score 0-1 before treatment and 14 patients with PS score 2 before treatment). Primary end point was overall survival (OS), and secondary end point were progression-free survival time (PFS), disease control rate (DCR), one-year survival, and drug toxicity. Survival analysis was evaluated by Kaplan-Meier. Single factor analysis and Cox regression model were done to analyze the relationship between the influencing factors and the prognosis of disease.The median PFS of the single-agent group was 3.0 months, significantly shorter than that of the combination group (4.2 months, P = 0.048). However, no statistical differences were found in OS, DCR or one-year survival between the two groups (all P0.05). The most common grade 3 to 4 toxicities were leukopenia (32.5% for single-agent group, and 56.2% for combination group, P = 0.000), and gastro-intestinal toxicity (0 for single-agent group, and 4.5% for combination group, P = 0.000). Single factor analysis showed that the factors including radiotherapeutic history, operative history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC (all P0.05). Cox regression analysis demonstrated operative history (HR = 0.428, 95% CI: 0.261-0.701), PS score before treatment (HR = 1.919, 95% CI: 0.999-3.685), clinical stage (HR = 2.297, 95% CI: 1.427-3.696) and response to second-line treatment (HR = 0.318, 95% CI: 0.177-0.571) had effects on survival.To those well-selected patients, docetaxel plus platinum combination agent as the second-line treatment of advanced NSCLC significantly prolongs the progression-free survival. But such a regimen is more toxic and does not improve the response rate and overall survival.

Background: Pigs are currently considered the most likely source of organs for human xenotransplantation because of anatomical and physiological similarities to humans, and the relative ease to be bred in large numbers. Along with the fast development of the genetic engineering and organ transplant immunity medical science, the research of liver xenotransplantation suffers the very big valuing in recent years. Whether the livers from different species after transplanting can perform the normal function, depends on the function regeneration and lucid rates of hepatic portal vein. The objective of this study was to investigate the age effect on biomechanical properties of pig hepatic portal vein to pave the way for seeking a reliable biomaterial for future pig-to-human liver xenotransplantation. Methods: The biomechanical remodelling of the hepatic portal vein of pigs for 1,2,3,4,5 and 6 months (n = 6 per month) were measured in this study. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The incremental modulus (Einc), the longitudinal incremental modulus (Ep), the circumferential incremental modulus (Ev), incremental compliance (C) and wall thickness were calculated based on the recorded pressure–diameter curves from experimental data. Results: The incremental modulus, pressure strain modulus and the volume modulus of the pig hepatic portal vein increases with the age increased (P

To observe the therapeutic effect and influential factors of strong stimulation of acupoints around eyes by reducing method of twisting the needle for treatment of adolescent myopia, and to compare the different curative effects of both weak and strong stimulus intensities and wearing glasses in daytime.According to the principle of knowing and permission, the patients were divided into a strong stimulation group (60 cases, 120 eyes), a weak stimulation group (60 cases, 120 eyes) and a wearing glasses group (60 cases, 120 eyes). Both the strong stimulation group and the weak stimulation group were treated by reducing method of twisting the needle, with Cuanzhu (BL 2), Yuyao (EX-HN 4), Sizhukong (TE 23), Sibai (ST 2) and Taiyang (EX-HN 5) selected. Each acupoint was twisted 360 and 90 times per min for the strong stimulation group, and 90 degrees and 60 times per min for the weak stimulation group; the wearing glasses group were not treated with acupuncture, but with wearing glasses in daytime.After treatment with the reducing method of twisting the needle, the vision improved (P0.01), with more obviously increased in the strong stimulation group than the weak stimulation group (P0.01), and there was no significant change of vision in the wearing glasses group. The age and the myopic degree of the patient before treatment were closely related with the change of vision after treatment (P0.01).The reducing method of twisting the needle has a definite clinical therapeutic effect on adolescent myopia; strong stimulation has a better effect than the weak one; the age and the myopic degree of the patient possibly influence the therapeutic effect.

Chronic prostatitis (CP) is a common disease among adult men. It can result in male infertility mainly by alternating the semen quality, volume, pH, component, viscosity and liquefaction. There seems to be a strong association between CP and semen delayed liquefaction. Researches on the mechanism of semen delayed liquefaction resulting from CP mainly focus on the proteolytic ferment, plasminogen activator, prostate acid phosphatase, tissue factor, lack of zinc, and pH. This article briefly reviews the progress in these aspects.

Novel polymer monolith microextraction (PMME) using a poly(methacrylic acid-ethylene glycol dimethacrylate) (poly(MAA-EGDMA)) monolith in conjunction with capillary zone electrophoresis (CZE) was developed for the determination of several angiotensin II receptor antagonists (ARA-IIs) in human urine. The extraction device consisted of a regular plastic syringe (1 mL), a poly(MAA-EGDMA) monolithic capillary (2 cm x 530 microm I.D.) and a plastic pinhead connecting the former two components seamlessly. The extraction was achieved by driving the sample solution through the monolithic capillary tube using a syringe infusion pump, and for the desorption step, an aliquot of organic solvent was injected via the monolithic capillary and collected into a vial for subsequent analysis by CZE. The best separation was realized at 25 kV using a buffer that consisted of 50% acetonitrile and 50% buffer solution (v/v) containing 10 mM disodium hydrogenphosphate (adjusted to pH 2.3 with 1M hydrochloric acid). The method was successfully applied to the determination of telmisartan (T), irbesartan (I) and losartan (L) in urine samples with candesartan (C) as internal standard, yielding the detection limit of 15-20 ng/mL. Close correlation coefficients (R>0.999) and excellent method reproducibility were obtained for all the analytes over a linear range of 0.08-3 microg/mL.

It had been observed that BRM-SJS had antitumor effect in our clinical practice. This study was designed to investigate the antitumor activity of BRM-SJS, and mechanism of its action.In vitro antitumor experiments with MTT method, meanwhile cell morphology, flow cytometry, and agarose gel electrophoresis were performed for determining apoptosis in several tumor cell lines.BRM-SJS had antitumor effects on human Suzhou human glioma (SHG-44), breast carcinoma (MCF-7), and human pancreas carcinoma (PANC1) in vitro, the IC50 values of BRM-SJS were 0. 299 mg/ml, 1.853 mg/ml and 9.416 mg/ml respectively. At the 2. 5 mg of BRM-SJS on SHG-44 and MCF-7, marked morphological changes, including cell shrinkage and condensation of chromosomes, were observed with electric microscope. The increase of apoptosis in SHG-44 and MCF-7 cells treated with BRM-SJS extracts 0.625 -2.5 mg for 14 -48 h was observed by Annexin-V/PI flow cytometry analysis. Agarose gel electrophoresis of DNA from SHG-44 and MCF-7 cells treated with BRM-SJS extracts 1.25 -5 mg for 24 h or 48 h showed marked DNA Ladder pattern.Antitumor activity of BRM-SJS may be related with inducement of apoptosis of tumor cells.

To explore the insulin resistance and first-phase insulin secretion of beta-cells in normal persons, obese persons with normal glucose tolerance, obese persons with impaired glucose tolerance (IGT) and obese persons with type 2 diabetes (T2DM).75 g oral glucose tolerance test (OGTT) and Bergman's minimal model method of frequently sampled intravenous glucose tolerance test (FSIGTT) with reduced sample number (n = 12) were performed on a total of 151 subjects, 29 normal controls (control group), 44 obese persons with normal glucose tolerance (obesity group), 36 obese persons with IGT (IGT group), and 42 T2DMT patients (T2DM group) to determine the acute insulin response to glucose (AIRg), insulin sensitivity index (S(I)), and glucose effectiveness (S(G)). The disposition index (DI, AIRg X S(I)) was calculated to determine whether AIRg was adequate to compensate for insulin resistance.The S(I) value of the control group was significantly higher than those of the obesity, IGT, and T2DM groups (all P0.01), without significant difference among the latter three groups. The S(G) value of the control group was not significantly different from that of the obesity group, but significantly higher than those of the IGT and T2DM groups (both P0.01), without significant difference any 2 groups from the latter two groups. The AIRg of the normal group was similar to that of the IGT group (2.61 mU x L(-1) x min(-1) +/- 0.13 mU.L(-1) x min(-1) vs 2.56 mU x L(-1) x min(-1) +/- 0.25 mU x L(-1) x min(-1)), and significantly lower than that of the obesity group (3.02 mU x L(-1) x min(-1) +/- 0.27 mU x L(-1) x min(-1), P0.01) and higher than that of the T2DM group (1.54 mU x L(-1) x min(-1) +/- 0.55 mU x L(-1) x min(-1), P0.01). The value of DI was gradually decreased from the sequence of the groups of control, obesity, IGT, and T2DM (3.16 +/- 0.31, 2.65 +/- 0.50, 1.67 +/- 0.54), with significant differences between any two groups (all P0.01). Multiple regression analyses with S(I) and AIRg as dependent variables showed that S(I) was negatively correlated with BMI, 2 h glucose level in OGTT, 2 h insulin, triglyceride, and cholesterol (r(2) = 0.589, P0.001), and AIRg was positively correlated with BMI, S(G), fasting insulin, and 2 h insulin level and negatively correlated with 2 h glucose, and age (r(2) = 0.515, P0.001).Obese patients with different glucose tolerance have similar degrees of insulin resistance. Acute insulin response is increased in obesity group to compensate for the insulin resistance. Although the acute insulin response in the IGT group is similar to that in the control group, however, the compensation of islet beta cells in the IGT group is significantly decreased as compared with that in the obesity group, leading to glucose intolerance. There is a severe deficiency of acute insulin response to glucose in T2DM group.

To investigate the relationship among fasting serum free fatty acid (FFA), insulin sensitivity index (ISI), serum triglyceride (TG) and total cholesterol (TC) levels in subjects with different body mass index (BMI) and glucose tolerance by using Bergman's minimodel method.26 normal control subjects, 39 obese subjects, 25 impaired glucose tolerance (IGT) subjects and 21 patients with newly diagnosed type 2 diabetes mellitus (DM) were recruited into this study. Serum FFA level was measured with radioimmunoassay and ISI was obtained by using Bergman's minimal model method.(1) In the four groups, serum FFA concentration of the control group was significantly lower than that of the other three groups, although there was no difference among the latter three. (2) ISI level of the control group was significantly higher than that of other three groups, while there was no difference among the latter three. (3) After adjusting with BMI, there was still significant difference in serum FFA levels between the control and the other three groups. (4) ISI, HOMAIR, BMI, waist hip ratio (WHR) and TG were all related to the concentration of serum FFA (r = -0.454, 0.213, 0.241, 0.336 and 0.414 respectively, P0.01,0.05,0.05,0.01 and0.01 respectively), while age, sex and serum TC levels were not related with serum FFA. (5) According to multivariate stepwise regression, ISI, BMI and TG were the major determinant factors for FFA (R(2) = 0.109, 0.212, 0.156, P0.001).Besides BMI, ISI and serum TG level are the major determinant factors that affect the concentration of serum FFA. As compared with the simple index HOMAIR, ISI level was more significantly related with serum FFA concentration. FFA levels are significantly different in various glucose tolerant states even after adjusting with BMI. FFA levels were obviously higher in subjects with IGT or type 2 diabetes mellitus.

To determine the relationship between a single point mutation in RET proto-oncogene and the occurrence of multiple endocrine neoplasia type 2B (MEN-2B) in a Chinese pedigree.We used the methods of polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR) and direct gene sequencing of PCR products by an automated DNA sequencer to scan the entire exon 16 of RET proto-oncogene in the tumor (c)DNA from one patient with MEN-2B and the leukocyte DNA from this patient and both of his parents.We found the same mutation Met(ATG)--Thr(ACG) at codon 918 in exon 16 of RET proto-oncogene in both the tumor (c)DNA and leukocyte DNA of the MEN-2B patient in the form of homozygous missense mutation, but there was no corresponding mutation in leukocytes DNA of his parents.We propose that in Chinese population, the point mutation M918T is also associated with the onset of MEN-2B and this case of MEN-2B is sporadic. Thus it may provide a genetic basis for the early diagnosis and treatment of patients suffering from MEN-2B and their at-risk family members in Chinese population.