Clinical significance of regulatory T cells and T lymphocyte subsets in peripheral blood in neoadjuvant chemotherapy for breast cancer.

The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4+CD25+CD127lowTreg), T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3+, CD4+, CD4+/CD8+ ratio and NK cells were significantly decreased in patients with breast cancer (P < 0.05), while the levels of Treg and CD8+ cells were significantly increased (P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3+, CD4+, CD4+/CD8+ ratio and NK cell were reduced, while the level of Treg and CD8+ T cells gradually increased. Furthermore, we found a lower percentage of CD3+, CD4+, CD4+/CD8+ and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8+ T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3+, CD4+ and CD4+/CD8+ ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time (P < 0.05). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4+CD25+CD127lowTreg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.

Laboratory detection of SARS-CoV-2: A review of the current literature and future perspectives.

Nowadays, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose infectivity is awfully strong, has been a major global threat to the public health. Since lung is the major target of SARS-CoV-2, the infection can lead to respiratory distress syndrome (RDS), multiple organ failure (MOF), and even death. The studies on viral structure and infection mechanism have found that angiotensin-converting enzyme 2 (ACE2), a pivotal enzyme affecting the organ-targeting in the RAS system, is the receptor of the SARS-CoV-2 virus. Currently, the detection of SARSCoV-2 is mainly achieved using open plate real-time reverse-transcription polymerase chain reaction (RT-PCR). While open plate method has some limitations, such as a high false-negative rate, cumbersome manual operation, aerosol pollution and leakage risks. Therefore, a convenient method to rapidly detect SARS-CoV-2 virus is urgently and extremely required for timely epidemic control with the limited resources. In this review, the current real-time methods and principles for novel coronavirus detection are summarized, with the aim to provide a reference for real-time screening of coronavirus in areas with insufficient detection capacity and inadequate medical resources. The development and establishment of a rapid, simple, sensitive and specific system to detect SARS-CoV-2 is of vital importance for distinct diagnosis and effective treatment of the virus, especially in the flu season.

Research progress in breast cancer stem cells: characterization and future perspectives.

More and more studies have proved that there are a small number of cells with self-renewal and differentiation ability in breast tumors, namely breast cancer stem cells. Such cells play a key role in the initiation, development and migration of breast tumors. The properties of breast tumor stem cells are regulated by a range of intracellular and extracellular factors, including important signaling pathways, transcription factors, non-coding RNAs, and cytokines such as Hedgehog, Wnt, Notch, microRNA93, microRNA100, and IL-6. Tumor microenvironment (such as mesenchymal stem cells, macrophages and cytokines) plays an important role in the regulation of breast tumor stem cells. Using the keywords including "breast cancer stem cells", "signal pathway", "chemotherapy tolerance", and "non-coding RNA", "triple negative breast cancer", "inhibitors", this study retrieved the original articles and reviews published before October 3, 2021, from PubMed and WEB OF SCI database and this study performed a comprehensive review of them. After treatment, there is a correlation between the metastasis-prone nature and recurrence with breast cancer stem cells. The signaling pathway of breast cancer stem cells plays a significant role in activating the function of breast cancer cells, regulating the differentiation of breast cancer cells and controlling the division of breast cancer cells. This imbalance leads to the uncontrolled growth and development of breast cancer cells. Targeted therapy that blocks the corresponding pathway may become a new perspective for breast cancer treatment. In addition, corresponding therapeutic strategies can be used according to the expression characteristics of different molecular types of breast cancer stem cells. For ER-positive breast cancer, simultaneous endocrine therapy and targeted therapy of tumor stem cells may improve the efficacy of endocrine therapy. Trastuzumab therapy significantly reduces the risk of recurrence of HER2-positive breast cancer. For drug-resistant patients, combination therapy is required due to the different phenotypes of epithelial-mesenchymal transforming tumor stem cells. This study briefly reviews the research progress of breast cancer stem cell-related signaling pathways and their inhibitors, in order to provide a reference for breast cancer patients to obtain more effective clinical treatment.

Pathogenesis of COVID-19 and the quality control of nucleic acid detection.

The new coronavirus pneumonia (COVID-19) epidemic spread rapidly throughout the world. Considering the strong infectivity and clustering of COVID-19, early detection of infectious cases is of great significance to control the epidemic. Nucleic acid testing (NAT) plays an important role in rapid laboratory diagnosis, treatment assessment, epidemic prevention and control of COVID-19. However, since COVID-19 is caused by a new emerging virus and NAT for COVID-19 has not been clinically applied before, false negative results inconsistent with clinical diagnosis have appeared in clinical practice. Therefore, it is urgent to improve the sensitivity of NAT for COVID-19. This study aimed to summarize the current situation and prospect of NAT based on the latest findings on COVID-19 infection. Also, the quality control of sample collection was discussed. Hopefully, this study could help to improve the effectiveness of NAT for COVID-19.

Astragaloside IV prevents endothelial dysfunction by improving oxidative stress in streptozotocin-induced diabetic mouse aortas.

Oxidative stress serves a role in endothelial dysfunction exhibited by patients with diabetes mellitus. Astragaloside IV (AS-IV) is a major active ingredient of Radix Astragali, which is considered to exhibit vasoprotective effects through unknown mechanisms. Thus, the current study was performed to investigate the protective effects of AS-IV in streptozotocin (STZ)-induced endothelial dysfunction and to explore whether antioxidant mechanisms were involved. The protective effects of AS-IV on the endothelium-dependent relaxation and contraction of aortic rings were determined by isometric tension recordings. NADPH subunits and endothelial nitric oxide synthase (eNOS) expression was identified via western blotting. Superoxide dismutase and malondialdehyde levels were assayed using ELISA. Furthermore, the generation of reactive oxygen species (ROS) and nitric oxide (NO) was detected via dihydroethidium and 4,5-diaminofluorescein diacetate staining, respectively. The results revealed that STZ-injected mice exhibited increased aortic endothelium-dependent vasoconstriction and decreased vasorelaxation to acetylcholine. However, AS-IV treatment reversed these effects. NG-nitro-L-arginine was subsequently used to completely inhibit impaired relaxation. Accordingly, impaired NO generation was restored following AS-IV treatment by increasing eNOS phosphorylation levels. Furthermore, ROS formation was also depressed following AS-IV treatment compared with that in STZ-injected mice. AS-IV also decreased the expression of various NADPH subunits, including human neutrophil cytochrome b light chain, neutrophil cytosolic factor 1, NADPH oxidase (NOX)2, NOX4 and Rac-1. The results of the current study may provide novel evidence that diabetes-induced vascular injury arises from either the inhibition of eNOS or the activation of NOX-derived ROS generation. In addition, the results warrant further investigation into the application of AS-IV treatment, leading to the improvement of oxidative stress, in patients with diabetes exhibiting endothelial dysfunction.

Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males.

Recent years have seen a rising incidence of male infertility, mostly caused by the decline of sperm quality. The ratio of infertile males to infertile females has escalated from 3:7 in 2013 to current 5:5, which turns male infertility into the research focus of reproductive medicine. This study aimed to clarify the effect of reproductive tract infection by ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) on the DNA integrity and routine semen parameters of infertile males. A retrospective study was performed. A total of 259 infertile males who were treated at the Andrological Laboratory Examination and Reproductive Medicine Center in our hospital were analyzed. qRT-PCR was used to examine the infection status of CT and UU. According to the eligibility criteria, we evaluated the semen parameters and biochemical data of 253 men. Based on the results of PCR, the subjects were divided into four groups: Group I (CT positive, 63 cases), Group II (UU positive, 60 cases), Group III (CT positive and UU positive, 62 cases), and Group IV (no infection, 68 cases). DNA fragmentation index (DFI), sperm count, vitality and morphology, elastase level, seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed. Compared to Group IV, three groups (Group I, Group II and Group III) showed difference in semen volume, proportion of sperm with normal morphology, sperm motility, progressive motility, and vitality (P < 0.05). Compared to Group IV, Group II and Group III showed difference in DFI (P < 0.05). Compared to Group IV, Group II and Group III showed difference in elastase level (P < 0.05). VCL, VSL, VAP, WOB, ROS, TM, HDS showed differences between groups of abnormal/normal WBC (*P < 0.01).UU infection significantly increased the level of seminal leukocytes only in Group II, but not in the other three groups, indicating that UU is a factor to increase the level of seminal leukocytes. Compared with the normal leukocyte group, there were significant differences in total motility, forward motility and normal sperm ratio between the two groups. The proportion of sperm with abnormal morphology (mostly in the head) showed obvious difference between groups of high and normal seminal leukocytic levels. At the same time, in this study, SCGE and SCD verified that leukocytes could damage sperm DNA by increasing ROS, which ultimately affects male fertility.

Potential effects of COVID-19 on reproductive health: a mini review.

Coronavirus disease 2019 (COVID-19) is now a major public health problem worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is extremely strong. One major target of the virus is the lung, which can lead to death due to the development of respiratory distress syndrome and even multiple system organ failure. The possible pathophysiology by which SARS-CoV-2 affects the object is by way of the receptor, angiotensin-converting enzyme 2 (ACE2). From the study of the viral structure and infection mechanisms, researchers have discovered that the ACE2 acts as a receptor for SARS-CoV-2. According to previous studies, ACE2 is one of the key enzymes in the RAS system. Physiological functions can be found in angiosarcomas and in the kidney, liver, intestine and so on. Whether SARS-CoV-2 infection leads to male fertility impairment has recently received attention. Nevertheless, the association between SARS-CoV-2 infection and reproductive health is currently poorly understood. Using key words including "SARS-CoV-2", "reproductive health", "ACE2" and "2019-nCoV", we retrieved original articles and reviews from the PubMed and WEB OF SCI databases published before December 16, 2020 and performed a thorough review of them. Compared with females, we discovered that infected person with SARS-CoV-2 was higher in males. Men who were infected with SARS-CoV-2 may be easy to suffer from impaired reproductive health. These investigations would help for a comprehensive grasp of the relationship between SARS-CoV-2 infection and reproductive health.

Application of leukocyte subsets and sperm DNA fragment rate in infertile men with asymptomatic infection of genital tract.

BACKGROUND: About 15% of male infertility is due to genital tract infection and inflammation, some of them have no clinical symptoms, but manifested as leukocytospermia (LCS). Leukopenia will lead to functional impairment of male sperm and integrity damage of sperm morphology. A large amount of reactive oxygen species (ROS) produced by leukocytes can damage sperm nuclear DNA. The aim of this study was to investigate the correlation between leukocyte subsets and sperm DNA fragmentation rate in semen of infertile men with asymptomatic infection of genital tract. METHODS: One hundred and eight cases of infertile men were enrolled, who were admitted to our hospital from May 2016 to September 2018, and all had genital tract infections. After routine sperm analysis, realtime PCR was performed for detecting the infection of chlamydia trachoma (CT) and Ureaplasma urealyticum (UU). Furthermore, total leukocyte count in semen was evaluated by detection of CD45 molecules using immunocytochemistry. Flow cytometry was used for subset analysis, monocyte/macrophages were evaluated by CD14, and activated macrophages were evaluated by HLA-DR antigen. Sperm DNA fragmentation index (DFI) were evaluated by SCD method and 8-hydroxydeoxyguanosine (8-OHdG) expression were evaluated by chromatin diffusion method and TUNEL method; the correlation analysis was conducted between semen leukocyte subsets, sperm DNA fragment rate and conventional semen parameters. RESULTS: There was a significant correlation among the concentrations of cells expressing HLA-DR antigen and those expressing CD14 (P<0.01), but the concentrations of differential leukocyte subsets all had no significant correlation with sperm DFI, the percentage of 8-OHdG-expressing cells and routine semen parameters. The percentage of 8-OHdG-expressing sperm was positively correlated with the percentage of sperm fragments (r=0.42, P<0.01), and negatively correlated with sperm concentration (r=-0.32, P<0.01). After adjustment for possible confounders including age, abstinence time and smoking, the percentage of 8-OHdG-expressing sperms independently associated with sperm concentration (ß=-0.30; P=0.006) and DFI (ß=0.180, P=0.06). CONCLUSIONS: Among infertile men with genital tract infection, the sperm DFI is associated with decreased semen quality and not the concentration of differential leukocyte subsets.

The application of quality control circle to improve the quality of samples: A SQUIRE-compliant quality-improving study.

Since its application in medical institutions in China, quality control circle (QCC) has gained achievements in medical care and thus earned more attention from the administrative department of health.In order to improve the quality of laboratory specimens, we launched a QCC activity to solve the problems and evaluate the effect of it. The data of 30,105 unqualified specimens in our hospital were collected from February to June 2017. After the QCC activity, the data of 43,125 specimens taken from July to December 2017 were collected.The defect rate of the specimens before the QCC activity was 0.98% (297/30105), and after the QCC activity, it was 0.45% (193/43125), showing a significant statistical difference (P < .05). The achievement rate and improvement rate were 108.2% and 54.1%, respectively.After the implementation of QCC, the defect rate of specimens in clinical laboratories was significantly decreased, and the intangible factors were also improved, which demonstrated the positive effects of QCC on the quality control of specimens.

High BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma increases diagnostic efficacy in cytologically indeterminate thyroid nodules.

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.

Biological functions of circular RNAs and their roles in occurrence of reproduction and gynecological diseases.

Circular RNAs (circRNAs) are a large class of non coding endogenous RNAs in eukaryotic that are formed through 3'-5' ligation of a single RNA molecule. According to the different sources of the sequences, circRNA can be divided into three types: exon circRNA (ecRNA), intron circRNA (ciRNA), and exon-intron circRNA. Accumulating studies have shown that circRNAs are abundant, diverse, stable, and cell or tissue specific expression, etc. CircRNA plays a regulating role in gene expression, and an essential role in the process of biological development, such as miRNA sponges, endogenous RNAs and biomarkers, as well as critical role in the diagnosis of diseases. Studies have verified the interplay between circRNAs and the development of embryos, sperms, ovarian epithelial tumors, endometrial cancer and preeclampsia, suggesting the potential of circRNAs to become biomarkers or therapeutical targets for human diseases. In this paper, we reviewed the researches on circRNAs' characteristics, databases of circRNA, high-throughput sequencing of circRNA, and effect on reproductive and gynecological diseases.

Comparison of a Newly Developed HPV Genotyping Assay (Mojin HPV Kit) with Cobas 4800 HPV Test for Detection of High-Risk HPV in Specimens Collected in SurePath Solution.

BACKGROUND: Human papillomavirus (HPV) detection based on cervical cytology specimens is useful for cervical cancer screening. The aim of this study was to compare Mojin HPV kit (a newly developed HPV genotyping assay) with the Cobas 4800 HPV test in detecting high-risk (HR) HPV. METHODS: A total of 347 cervical exfoliated cell specimens were tested using the Mojin HPV kit and Cobas 4800 HPV test. When the results from the two tests were inconsistent, gene sequencing was performed for correction. RESULTS: For HR-HPV, the results of the two assays agreed by 96.3% [Kappa = 0.911; 95% confidence interval (CI): 0.863 - 0.958)]. The positive and negative coincidence rates between the two tests were 96.0% (95% CI: 92.7% - 98.0%) and 97.0% (95% CI: 91.5% - 99.4%), respectively. Of the 13 samples with discordant results, 3 samples were false positive and 10 samples were true negative for Mojin HPV test, according to the identification by sequencing. For HPV16 genotyping, the total coincidence rate between the 2 tests was 100% (Kappa = 1.000), and 99.7% (Kappa = 0.973; 95% CI: 0.905 - 1.000) for HPV18. CONCLUSIONS: Mojin HPV kit may be as effective as Cobas 4800 HPV assay in detecting the total HR-HPV, especially HPV16 or HPV18.

Correlation between plasma ferritin level and gestational diabetes mellitus and its impact on fetal macrosomia.

AIMS/INTRODUCTION: To explore the relationship between plasma iron levels and gestational diabetes mellitus, as well as its impact on macrosomia. MATERIALS AND METHODS: We retrospectively compared ferritin level and other characteristics between pregnant women with gestational diabetes mellitus (GDM) and pregnant women without GDM. The correlation between the levels of plasma ferritin, glucose and hemoglobin was explored. Meanwhile, we assessed the risk factors of macrosomia. Furthermore, we explored the relationship between ferritin level and the incidence of macrosomia. RESULTS: A total of 793 pregnant women were enrolled in the present study, of which 92 pregnant women had GDM and 701 pregnant women were healthy. Meanwhile, 51 pregnant women gave birth to infants with macrosomia and another 742 women had normal infants. Compared with non-GDM women, pregnant women with GDM were older, with higher pre-pregnancy body mass index, plasma ferritin, fasting plasma glucose, 1-h postprandial glucose, 2-h plasma glucose and hemoglobin. In addition, our results showed a significant positive correlation between the levels of ferritin and fasting plasma glucose when ferritin levels were >70 ng/mL. Our results also showed that pre-pregnancy overweight or obesity, a high concentration of ferritin, as well as abnormal levels of fasting plasma glucose, 1-h plasma glucose and 2 h plasma glucose were risk factors for macrosomia. Furthermore, as the level of ferritin increased, so did the incidence of macrosomia. CONCLUSIONS: The current study provides evidence that pregnant women with high levels of ferritin might be prone to GDM. In addition, a high level of ferritin might be an independent risk factor for macrosomia. Therefore, the negative effect of iron supplementation in non-anemic pregnant women might be noteworthy.

Advances of Long Noncoding RNAs-mediated Regulation in Reproduction.

OBJECTIVE: Advances in genomics and molecular biology have led to the discovery of a large group of uncharacterized long noncoding RNAs (lncRNAs). Emerging evidence indicated that many lncRNAs function in multiple biological processes and its dysregulation often causes diseases. Recent studies suggested that almost all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression mainly on three levels, including epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling. LncRNAs can also affect the development of diseases and therefore be used to diagnose and treat diseases. With new sequencing and microarray techniques, hundreds of lncRNAs involved in reproductive disorders have been identified, but their functions in these disorders are undefined. DATA SOURCES: This review was based on articles published in PubMed databases up to July 10, 2017, with the following keywords: "long noncoding RNAs", "LncRNA", "placentation", and "reproductive diseases". STUDY SELECTION: Original articles and reviews on the topics were selected. RESULTS: LncRNAs widely participate in various physiological and pathological processes as a new class of important regulatory factors. In spermatogenesis, spermatocytes divide and differentiate into mature spermatozoa. The whole process is elaborately regulated by the expression of phase-specific genes that involve many strains of lncRNAs. Literature showed that lncRNA in reproductive cumulus cells may contribute to the regulation of oocyte maturation, fertilization, and embryo development. CONCLUSIONS: LncRNA has been found to play a role in the development of reproduction. Meanwhile, we reviewed the studies on how lncRNAs participate in reproductive disorders, which provides a basis for the study of lncRNA in reproduction regulation.

Improvement of Huangqi Decoction on Endothelial Dysfunction in 5/6 Nephrectomized Rats.

BACKGROUND/AIMS: Endothelial dysfunction is a major factor in the progression of chronic kidney disease, which correlates with oxidative stress and NO deficiency. Huangqi decoction (HQD) is a potential anti-oxidant ingredient in renoprotection. However, the underlying mechanisms remained identified. Therefore, we investigated whether HQD exhibit improvement in endothelial dysfunction in the 5/6 nephrectomy (Nx) rat model. METHODS: Male Wistar rats (180 - 250 g) were divided into sham, Nx and Nx + HQD (0.05, 0.15 and 0.45 g/kg) group, respectively. Renal function and histology were examined with ELISA and Immunohistochemical analysis. Endothelium-dependent relaxation of rat aortas was investigated by isometric tension recordings. Oxidative stress and NO bioavailability were detected by ELISA, DHE-staining, DAF-2 staining and western blotting. RESULTS: Compared with Nx rats, HQD treatment reversed the functional and structural changes of kidney significantly. Besides, endothelium-dependent relaxation of rat aortas was also improved by HQD treatment. NADPH oxidase and ROS generation were inhibited while NO bioavailability was enhanced. CONCLUSION: HQD can act as a potent prescription for the treatment of endothelium related vascular complications.

Effects of Huang Qi Decoction on Endothelial Dysfunction Induced by Homocysteine.

Vascular endothelial dysfunction can be induced by homocysteine (Hcy) through promoted oxidative stress. Huang Qi decoction (HQD) is a traditional Chinese medical formula and its components possess antioxidant effect. The study herein was therefore designed to investigate the effects of HQD at different dosage on endothelial dysfunction induced by Hcy. Tempol and apocynin were used to investigate whether antioxidant mechanisms were involved. Endothelium-dependent relaxation of rat aortas was investigated by isometric tension recordings. Reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs) was determined by DHE staining. The assessment related to oxidative stress and NO bioavailability was performed by assay kits and western blot. In isometric tension experiment, HQD at the dose of 30 or 100 µg/mL, tempol, or apocynin prevented impaired endothelium-dependent relaxation in isolated aortas elicited by Hcy. In cellular experiments, substantial enhancement in NADPH oxidase and ROS generation and reduction in NO bioavailability triggered by Hcy were reversed by pretreatment of HQD at the dose of 100 µg/mL, tempol, or apocynin. The results proved that HQD at an appropriate dosage presented favorable effects on endothelial dysfunction initiated by Hcy through antioxidant mechanisms. HQD can act as a potent prescription for the treatment of endothelium related vascular complications.

Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Bevacizumab and erlotinib inhibit different tumour growth pathways, and both exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC. METHODS: Randomised controlled trials (RCTs) published in PubMed, Web of Science and EMBASE were systematically reviewed. The main outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events. Results were expressed as HRs or risk ratios (RRs) with 95% CIs. RESULTS: 5 RCTs involving a total of 1736 patients were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19 to 3.06; p=0.007) in the second-line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95% CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI 0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI 0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhoea was higher in the combination group than in the monotherapy group. CONCLUSIONS: The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea. Further well-conducted, large-scale trials are needed to validate these findings.

Towards prenatal biomonitoring in Nanjing, China: lead and cadmium levels in the duration of pregnancy.

BACKGROUND: Prenatal lead and cadmium exposure will not only influence the mother' organ systems, but also will provide an environment that may influence the fetus and neonate in a harmful way.In the present study, we detected the blood lead levels (BLLS) and cadmium levels for the duration of pregnancy and 6-12 weeks after delivery and to analyze the influencing factors of BLLs in healthy pregnant women. METHODS: A cohort study survey was carried out. We recruited 174 healthy pregnant women without pregnancy or obstetric complications or abnormal pregnancy outcomes as the gravida group, and 120 healthy non-pregnant women as the control group. RESULTS: The lead concentrations in the three pregnancy trimesters and in the postpartum period were: (5.98 ± 2.43), (5.54 ± 2.01), (5.59 ± 1.97), and (6.76 ± 1.74) µg/dl; and (6.75 ± 2.13) µg/dl in the control group. The cadmium concentrations in the three pregnancy trimesters and postpartum period were 1.61 ± 0.45, 1.63 ± 0.46, 1.64 ± 0.49, and 1.67 ± 0.57. We found that the BLLs in the gravida group were lower than in the control group during all three trimesters. Occupations, supplement nutritional elements (dietary supplements and nutritional (food) elements), and the time of house painting could affect BLLs in pregnant women. Lead-related occupations, using cosmetics, and living in a house painted more recently than one year previously are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors. CONCLUSIONS: These findings may help people, especially pregnant women, to reduce lead exposure via supplements of calcium, iron, zinc, and milk or avoiding contacting risk factors.

[Homing of CFSE-labeled antigen-specific CD4(+)CD25(+) regulatory T cells in islets transplantation].

AIM: To observe the distribution and proliferation of the antigen-specific CD4(+)CD25(+) regulatory T (Treg ) cells and investigate the potential mechanism of antigen-specific CD4(+)CD25(+) regulatory T cells on the suppression of rejection for allogenetic islet transplantation in vivo. METHODS: Antigen-specific CD4(+)CD25(+) Treg cells were generated by the addition of multiple intravenous injections of ICR mice splenocytes in vivo. After labeled by CFSE, 8x10(5) antigen-specific Treg cells were injected via tail vein with islets transplantation. Homing and distribution of antigen-specific CD4(+)CD25(+) Treg cells were investigated by flow cytometric analysis and immunofluorescence. RESULTS: In vivo, the mean survival time of recipients with islets and antigen-specific CD4(+)CD25(+) Treg cells were (34.57+/-17.15) days, whereas transplanted islets without Treg treatment survived (10.6+/-1.82) days in control mice. The transferred antigen-specific CD4(+)CD25(+) Treg cells were mainly resident in pancreatic node and mesenteric node. CONCLUSION: Allogeneic antigen-specific CD4(+)CD25(+) Treg cells prolong islet graft survival, and draining lymphoid tissue play a key role in the immune response.

Effect of taurine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes.

BACKGROUND: Activations of death receptors and mitochondrial damage are well-described common apoptotic pathways. Recently, a novel pathway via endoplasmic reticulum (ER) stress has been reported. METHODS: We assessed the role of tauroursodeoxycholic acid (TUDCA) in inhibition of ER stress and its protective effect on advanced glycation end products (AGEs)-induced apoptosis in murine podocytes. Podocytes were incubated with increasing doses of AGEs for variable time periods. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously. Level of glucose-regulated protein 78 (ER stress marker) expression was determined by Western blot. Intracellular calcium concentration ([Ca(2+)](i)) was recorded by a laser confocal microscope and the Ca(2+) indicator Fluo-3 labeling. RESULTS: AGEs induced podocyte apoptosis and increased the expression of glucose-regulated protein 78 in a dose- and time-dependent manner as compared with bovine serum albumin. These changes were accompanied by a rapid rise in [Ca(2+)](i) of podocytes. TUDCA was capable of abolishing AGEs-induced expression of glucose-regulated protein 78 and subsequently inhibited apoptosis in a dose-dependent manner. CONCLUSION: We propose that ER stress plays an important role in AGEs-induced apoptosis and that TUDCA prevents apoptosis by blocking an ER stress-mediated apoptotic pathway. This novel mechanism of TUDCA action suggests new intervention methods for AGEs-induced apoptosis of mouse podocytes in diabetic nephropathy.