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To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older.This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression.Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P0.001] and a significantly lower probability of survival (P0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19.The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

How cells control gene expression is a fundamental question. The relative contribution of protein-level and RNA-level regulation to this process remains unclear. Here, we perform a proteogenomic analysis of tumors and untransformed cells containing somatic copy number alterations (SCNAs). By revealing how cells regulate RNA and protein abundances of genes with SCNAs, we provide insights into the rules of gene regulation. Protein complex genes have a strong protein-level regulation while non-complex genes have a strong RNA-level regulation. Notable exceptions are plasma membrane protein complex genes, which show a weak protein-level regulation and a stronger RNA-level regulation. Strikingly, we find a strong negative association between the degree of RNA-level and protein-level regulation across genes and cellular pathways. Moreover, genes participating in the same pathway show a similar degree of RNA- and protein-level regulation. Pathways including translation, splicing, RNA processing, and mitochondrial function show a stronger protein-level regulation while cell adhesion and migration pathways show a stronger RNA-level regulation. These results suggest that the evolution of gene regulation is shaped by functional constraints and that many cellular pathways tend to evolve one predominant mechanism of gene regulation at the protein level or at the RNA level.

Background: Lung cancer is the leading cause of death among cancer patients worldwide. Close to 85% of lung cancer pathology types are nonsmall cell lung cancer (NSCLC). With advances in medicine, the survival rate of early-stage NSCLC has improved. Nevertheless, about 70% of patients are diagnosed at an advanced stage, and chemotherapy is the primary treatment option. Chemotherapy causes toxic side effects such as bone marrow suppression, gastrointestinal reactions, and damage to vital organs, which are difficult for patients to tolerate. Many published literatures have reported that Shenmai injection (SMI) combined with platinum-containing first-line chemotherapy regimen for NSCLC can improve the recent efficacy, reduce toxic side effects and improve the quality of life. However, most of the studies were small samples and lacked persuasive power, while controversies existed among individual studies. Therefore, this study used meta-analysis to further evaluate the effects of SMI combined with platinum-containing first-line chemotherapy on the quality of life, immune function and prognosis of patients with NSCLC. Methods: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases were searched. The search was scheduled from the establishment of the database to September 2021. All randomized controlled trials comparing SMI in combination with platinum-containing first-line chemotherapy to platinum-containing first-line chemotherapy alone for the treatment of NSCLC were searched and evaluated for inclusion. Two investigators independently performed study selection, data extraction and synthesis. The Cochrane Risk of Bias tool was used to assess the risk of bias in the randomized controlled trials. Stata 16.0 software was used for meta-analysis. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: This study comprehensively evaluated the effects of SMI combined with platinum-containing first-line chemotherapy on quality of life, immune function and prognosis in patients with NSCLC to provide an evidence-based basis for clinical practice. Ethics and dissemination: The private information from individuals will not be published. This systematic review should also not damage participants’ rights. Ethical approval was not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF Registration number: DOI 10.17605/OSF.IO/AMKDC

To explain the observed phenomenon that most SARS‐CoV‐2 transmission occurs indoors whereas its outdoor transmission is rare, a simple macroscopic aerosol balance model is developed to link short‐ and long‐range airborne transmission. The model considers the involvement of exhaled droplets with initial diameter ≤50 µm in the short‐range airborne route, whereas only a fraction of these droplets with an initial diameter within 15 µm or equivalently a final diameter within 5 µm considered in the long‐range airborne route. One surprising finding is that the room ventilation rate significantly affects the short‐range airborne route, in contrast to traditional belief. When the ventilation rate in a room is insufficient, the airborne infection risks due to both short‐ and long‐range transmission are high. A ventilation rate of 10 L/s per person provides a similar concentration vs distance decay profile to that in outdoor settings, which provides additional justification for the widely adopted ventilation standard of 10 L/s per person. The newly obtained data do not support the basic assumption in the existing ventilation standard ASHRAE 62.1 (2019) that the required people outdoor air rate is constant if the standard is used directly for respiratory infection control. Instead, it is necessary to increase the ventilation rate when the physical distance between people is less than approximately 2 m.

An aneuploid-immune paradox encompasses somatic copy-number alterations (SCNAs), unleashing a cytotoxic response in experimental precancer systems, while conversely being associated with immune suppression and cytotoxic-cell depletion in human tumors, especially head and neck cancer (HNSC). We present evidence from patient samples and cell lines that alterations in chromosome dosage contribute to an immune hot-to-cold switch during human papillomavirus-negative (HPV(−)) head and neck tumorigenesis. Overall SCNA (aneuploidy) level was associated with increased CD3(+) and CD8(+) T cell microenvironments in precancer (mostly CD3(+), linked to trisomy and aneuploidy), but with T cell-deficient tumors. Early lesions with 9p21.3 loss were associated with depletion of cytotoxic T cell infiltration in TP53 mutant tumors; and with aneuploidy were associated with increased NK-cell infiltration. The strongest driver of cytotoxic T cell and Immune Score depletion in oral cancer was 9p-arm level loss, promoting profound decreases of pivotal IFN-γ-related chemokines (e.g., CXCL9) and pathway genes. Chromosome 9p21.3 deletion contributed mainly to cell-intrinsic senescence suppression, but deletion of the entire arm was necessary to diminish levels of cytokine, JAK-STAT, and Hallmark NF-κB pathways. Finally, 9p arm-level loss and JAK2-PD-L1 codeletion (at 9p24) were predictive markers of poor survival in recurrent HPV(−) HNSC after anti–PD-1 therapy; likely amplified by independent aneuploidy-induced immune-cold microenvironments observed here. We hypothesize that 9p21.3 arm-loss expansion and epistatic interactions allow oral precancer cells to acquire properties to overcome a proimmunogenic aneuploid checkpoint, transform and invade. These findings enable distinct HNSC interception and precision-therapeutic approaches, concepts that may apply to other CN-driven neoplastic, immune or aneuploid diseases, and immunotherapies.

Vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) along a vertical column of flats has been documented in several outbreaks of coronavirus disease 2019 (COVID-19) in Guangdong and Hong Kong. We describe an outbreak in Luk Chuen House, involving two vertical columns of flats associated with an unusually connected two-stack drainage system, in which nine individuals from seven households were infected. The index case resided in Flat 812 (8th floor, Unit 12), two flats (813, 817) on its opposite side reported one case each (i.e., a horizontal sub-cluster). All other flats with infected residents were vertically associated, forming a vertical sub-cluster. We injected tracer gas (SF

Introduction: There are many injection methods for the treatment of knee osteoarthritis, but there is no comprehensive comparison, based on the fixed effect model. Methods: According to the retrieval strategy, we searched randomized controlled trials (RCTs) randomly from PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), Wanfang Database from their inceptions to August 2020, and 2 members of us selected literatures and extracted data independently. Methodological quality was assessed by using the Cochrane bias risk tool, and meta-analysis was performed by using the Stat.14.0. Results: This study will evaluate the effectiveness and safety of different injectable drugs for the treatment of knee osteoarthritis and rank the efficacies of drugs, then to determine the optimal treatment. Conclusion: This study will provide evidence for the choice of injection therapy for knee osteoarthritis. INPLASY registration number: INPLASY202080099.

Introduction: Traditional Chinese medicine has been widely used in the treatment of allergic rhinitis. However, currently randomized controlled trials (RCTs) and meta-analysis only compare 1 or 2 types of traditional Chinese medicine therapies, and the comprehensive ranking of efficacy and safety of multiple traditional Chinese medicine therapies for the treatment of allergic rhinitis has not been completed. Therefore, the purpose of this network meta-analysis is to evaluate the efficacy and safety of different traditional Chinese medicine therapies for the treatment of allergic rhinitis. Methods and analysis: Three English databases of PubMed, Embase, Cochrane Library, and 2 Chinese databases of CNKI and Wanfang were searched from their inceptions to September 1, 2020. At the same time, in order to prevent omissions, we also compared the previous meta-analysis to determine the final included trials. The main evaluation outcome was the total Clinical Score (total nasal symptom score [TNSS]), the secondary evaluation outcome was the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and adverse events. The Cochrane Collaboration's Tool was used to evaluate the methodological quality of articles, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument was used to evaluate the quality of evidence. Network meta-analysis was completed by using Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX). Results: This study will compare and rank the different traditional Chinese medicine therapies for allergic rhinitis. Conclusion: This study is the first time to use network meta-analysis (NMA) to compare the efficacy and safety of traditional Chinese medicine for the treatment of allergic rhinitis, which will provide ideas and methods for the clinical treatment for allergic rhinitis. INPLASY registration number: No. INPLASY202080119

Background: Anxiety and depression, complications of cancer, are prevalent but often overlooked mental illnesses. Studies have demonstrated that massage therapy is useful in relieving anxiety and depression of cancer survivors. However, the mechanism is still unclear and no systematic review has provided sufficient evidence for the treatment. Therefore, this protocol is carried out to comprehensively evaluate the reliability of cancer patients with anxiety and depression treated by massage. Methods: We will systematically search the relevant literature from PubMed, Cochrane Library, EMBASE, Web of Science, Wanfang, Chongqing VIP, CNKI and Chinese Biomedical Literature Database from the establishment of the databases to June 1, 2020. In addition, we will only include randomized controlled trials about massage for cancer survivors with anxiety and depression, regardless of language and publication status. Two experienced researchers will separately screen the literature, collect data, analyze data and synthesize data using RevMan V.5.3 software. The quality of the included trials in the study will be assessed by the Cochrane bias risk assessment tool. Results: The protocol for the meta-analysis will systematically evaluate the reliability of massage therapy for cancer patients with anxiety and depression. Conclusion: This conclusion will provide an important basis for evaluating whether massage is reliable in treating cancer survivors who feel anxious and depressed. INPLASY registration number: INPLASY202060101

Background Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. Methods Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. Results The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. Conclusion Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.

To investigate the exprassion of WT1 gene in patients with adult acute myeloid leukemia (AML) and its clinical significance.Sixty-three newly diagnosed patients with acute myeloid leukemia were selected. Quantitative RT-PCR was used to detect the expression of WT1 gene in the 63 AML patients and 20 non-AML controls.WT1 gene was highly expressed in AML patents and its expression in the low-risk group was significantly lower than that in middle-risk group and high-risk group (P0.05), and no significant difference of WT1 gene expression between middle-risk and high-risk group was observed. In the patients of middle-risk and high-risk patients, the expression of WT1 gene in the remission group was significantly lower than that in the patients of non-remission after treatment (P0.05). The non-remission patients after first treatment in middle-risk and high-risk group were treated with second induction therapy. After second induction therapy, the WT1 expression in remission patients was significantly decreased (P0.05) in comparison with that in patients still in non-remission. There was a negative correlation between WT1 expression and the 2-year overall survival rate in the newly diagnosed middle and high-risk AML patients.The detection of WT1 gene expression can help to divide AML patients into low-/middle-/high-risk groups and to evaluate therapeutic response and clinical prognosis in middle and high-risk AML patients.

Background: This study will evaluate the clinical effect of vestibular rehabilitation (VR) on benign paroxysmal positional vertigo (BPPV). Methods: In this study, we will identify relevant trials on the topic published in MEDLINE, EBASE, Web of Science, Cochrane Library, Scopus, CINAHL, CBM, and CNKI from inception to the present. We will also search conference proceedings, thesis/dissertation, ongoing trials in clinical trial registry, and reference lists of included studies. Two researchers will independently carry out record selection, data extraction, and study quality assessment, respectively. Any disagreement will be arbitrated and solved with the help of a third researcher. If necessary, we will conduct random-effects meta-analysis to pool the effect estimates of included trials determined to be acceptable heterogeneity. Results: We will summarize the latest evidence to assess the effect of VR for the treatment of patients with BPPV. Conclusion: The findings of this study will help determine whether or not VR is effective in treating BPPV. OSF registration: osf.io/k83y5.

Background: Knee osteoarthritis (KOA), a concerning public health problem, seriously threatens well being of human beings. At present, studies have shown that massage therapy is effective in relieving related symptoms of KOA. However, the evidence of massage for KOA has not been systematically evaluated. Therefore, the study is conducted to systematically assess the reliability of patients with KOA treated by massage. Methods: We will retrieve the relevant literature of massage for KOA from PubMed, Cochrane Library, EMBASE, Web of Science, Wanfang, Chongqing VIP, CNKI, and Chinese Biomedical Literature Database from the establishment of the databases to August 1, 2020. Two researchers will independently perform the screening of literature and extract the basic information of the data. In addition, RevMan V.5.3 software will be used for data analysis. Results: The study will comprehensively assess the effect of massage for KOA. Conclusion: The study will provide comprehensive evidence for evaluating whether massage therapy is useful in treating patients with KOA. INPLASY registration number: INPLASY202080115.

Background: With the rising incidences stroke, the Post-Stroke Urinary Incontinence (PSUI) has become one of the common clinical sequelae. PSUI not only lowers the quality of life of patients, but also impacts tremendously to mental health. As a treasure of Chinese medicine, acupuncture and its related therapies have been widely accepted in clinical treatment of PSUI. Recently, there have been many clinical studies on the treatment of PSUI with acupuncture and related therapies, but the best way to treat PSUI is controversial. Therefore, the purpose of this paper is to provide an optimal ranking regarding acupuncture and its related therapies for PSUI. Methods: The five domestic and foreign databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database will be systematically searched. The time range of the literature search is from the date of establishment to August 31, 2020. The main evaluation outcome was the number of patients after treatment, and the frequency of urinary incontinence. The secondary evaluation outcome was International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Barthel Activities of Daily Living Index (Barthel ADL Index) and the incidence rate of adverse events. The methodological quality of the article will evaluated by Cochrane Collaboration's Tool and the quality of evidence will evaluated through Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. The Network Meta-Analysis (NMA) will be completed using Stata statistical software. Results: The final results of this study will be published in a peer-reviewed journal. Conclusion: This network meta-analysis will compare the efficacy and safety of different acupuncture therapies in the treatment of PSUI and summarize the best treatment options, which will help patients and doctors to choose effective acupuncture methods in time.

Circulating tumor cells (CTCs) play a key role in cancer metastasis but are very difficult to detect. in vivo monitoring CTCs has been recognized as an important technique for cancer research and clinical diagnosis. Recently, a noninvasive method, in vivo flow cytometry (IVFC) has been developed to enable continuous, real-time, and long-duration detection of CTCs in animal models by detecting CTC fluorescence in blood vessels excited by lasers. In this study, we present a simple optical scheme for direct noninvasive CTC detection using confocal microscopes. We demonstrate that line scanning of confocal microscopy can provide effective and quantitative CTC detection in live mice during cancer development. Rare CTC signals can be acquired at the early stage of the tumor development after implantation of subcutaneous tumor and monitored continuously to the end. Signals from CTC clusters can also be acquired and distinguished from single CTCs. Our results suggest confocal microscopy is a simple and reliable method for biologists and doctors to use for cancer research. © 2018 International Society for Advancement of Cytometry.

Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation. Among 50 natural compounds, aculeatiside A, naringin, and onionin A significantly induced the CD169-positive phenotype in human monocyte-derived macrophages. These compounds also induced CD169 overexpression and secretion of inflammatory cytokines, including interleukin (IL)-1β and IL-12, in murine macrophages. Subcutaneous injection of aculeatiside A and naringin enhanced mRNA expression of IL-1β, IL12, and CD169 in regional lymph nodes in mice. These findings suggest aculeatiside A and naringin may enhance anti-tumor immune responses by inducing CD169-positive macrophages in lymph nodes.

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS.

Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here, we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histologic grade. We observed macrophage-induced tumor cell proliferation in cocultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison with wild-type (WT) mice. Coculture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison with WT macrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL6 and CXCL2. Silencing of IL6 but not CXCL2 abrogated macrophage-induced proliferation of MCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans. Significance: Macrophage CD163-mediated induction of IL6 promotes tumor development and progression in murine and human malignant tumors. Cancer Res; 78(12); 3255–66. ©2018 AACR.

Widespread use of pentachlorophenol (PCP) in schistosomiasis endemic areas had led to ubiquitous exposure to PCP and its residues. Numerous studies had revealed that occupational PCP exposure probably increased risk of cancers, but whether long-term community-level exposure to PCP generates the similarly carcinogenic effect, seldom studies focused on it. This study was to explore the cancer risks of long-term community-level PCP exposure from drinking water in a Chinese general population. Incident (2009-2012) cancer records were identified by local government national registry. And PCP concentration of raw drinking water samples in each district was measured by GC-MS/MS analysis for further division of three PCP exposure categories by interquartile range (high vs. medium vs. low). Internal comparisons were performed, and standard rate ratio was calculated to describe the relationship between PCP exposure and cancer risks by using low-exposure group as the reference group. PCP was detected in all 27 raw drinking water samples ranging from 11.21 to 684.00 ng/L. A total of 6,750 cases (4,409 male and 2,341 female cases) were identified, and age-standardized rate (world) was 154.95 per 100,000 person-years. The cancer incidence for the high-exposure group was remarkably high. Internal comparisons indicated that high PCP exposure might be positively associated with high cancer risks in the community population, particularly for leukemia (SRR = 5.93, 95 % CI = 5.24-6.71), maligant lymphoma (SRR = 2.27, 95 % CI = 2.10-2.54), and esophageal cancer (SRR = 2.42, 95 % CI = 2.35-2.50). Long-term community-level exposure to PCP was probably associated with hemolymph neoplasm, neurologic tumors, and digestive system neoplasm.

As an important methyltransferase, DNMT1 plays a key role in DNA methylation that is essential for normal spermatogenesis, which suggests that it may be involved in male infertility with spermatogenesis impairment. To explore the relationship between DNMT1 and spermatogenesis impairment, polymorphic distributions of single-nucleotide polymorphisms (SNP) rs16999593, rs2228612 and rs2228611 in DNMT1 were investigated in 342 infertile patients with idiopathic azoospermia or oligospermia and 232 fertile controls in a Chinese population. As a result, no significant differences in allele and genotype frequencies of the three SNP between total patients and controls were observed. However, after stratifying the patients, significant differences in allele and genotype frequencies were detected between oligospermia subgroup and control group. The frequencies of rs16999593 allele A (83.6% versus 77.6%, P =0.033) and genotype AA (69.2% versus 59.0%, P =0.037) and SNP rs2228611 genotype AA (18.4% versus 9.9%, P =0.016) in patients with oligospermia were significantly higher than those in control group. These findings suggest that the polymorphism in DNMT1 might be associated with oligospermia and could modify the susceptibility of oligospermia. The DNMT1 gene plays a key role in DNA methylation, which is essential for normal spermatogenesis, and it may be involved in male infertility with spermatogenesis impairment. To explore the possible relationship between DNMT1 and spermatogenesis impairment, polymorphic distributions of the single-nucleotide polymorphisms (SNP) rs16999593, rs2228612 and rs2228611 in DNMT1 were investigated in 342 infertile patients with idiopathic azoospermia or oligospermia and 232 fertile controls in a Chinese population. As a result, the frequencies of allele A and genotype AA of SNP rs6999593 and of genotype AA of SNP rs2228611 were significantly higher in patients with oligospermia than in controls. These findings suggest that the polymorphism of DNMT1 might be associated with oligospermia and could modify the susceptibility of oligospermia.

KIT/KITLG signaling system is crucial for spermatogenesis, which suggests that KIT and KITLG genes may be involved in spermatogenesis impairment and male infertility. To explore the possible association of KIT and KITLG genes with male infertility having spermatogenesis impairment, polymorphism distributions of SNP rs3819392 in KIT gene as well as rs995030 and rs4474514 in KITLG gene were investigated in 372 patients with idiopathic azoospermia or oligospermia and 205 fertile controls. As a result, the significant differences in polymorphism distributions of SNP rs3819392 in KIT gene and rs4474514 in KITLG gene were observed between the patients with oligospermia and controls. The frequencies of allele G (94.2% versus 90.0% p = 0.022) and genotype GG (89.2% versus 82.0% p = 0.042) in patients with oligospermia were significantly higher than those in controls at rs3819392 locus in KIT gene. In addition, the genotype CC of rs4474514 in KITLG (8.2% versus 3.4%, p = 0.034) also significantly increased in oligospermic patients in comparison to controls. These findings indicated that SNP rs3819392 in KIT gene and rs4474514 in KITLG gene may be associated with oligospermia, suggesting that polymorphism of KIT and KITLG genes may play a role in oligospermia.

The immunosuppressive effect and low immunogenicity of mesenchymal stem cells (MSCs) make them ideal candidates for immunosuppressive strategies. Adult MSCs have been applied widely in organ transplantation. However, their limited accessibility limits their application in the clinic. Furthermore, successive passages slow the proliferation rate, reduce the multipotency and lower the immunosuppressive activity of adult MSCs in culture. Induced pluripotent stem cells-derived MSCs (iPSC-MSCs) may provide an alternative source of MSCs. iPSC-MSCs have the same characteristics as adult MSCs and exhibit great immunomodulatory properties. For example, iPSC-MSCs displayed significant inhibition of NK cell proliferation and cytolytic function [1]. iPSC-MSCs modulated T-cell phenotypes towards Th2 suppression and induced T regulatory cell (Treg) expansion in the peripheral blood from allergic rhinitis patients [2]. And the similar therapeutic effects on Th2 cytokines were observed in a mouse model of ovalbumin-induced allergic inflammation [3]. Given the great immunomodulatory properties of the iPSC-MSCs, we speculated that iPSC-MSCs could be a promising strategy for preventing transplant rejection. Indeed, we found that iPSC-MSCs combined with low-dose rapamycin (Rapa, 0.1 mg/kg/d, i.p., from day 0 to day 9) significantly prolonged islet allograft survival in the diabetic mice, and even induced immune tolerance in 50% recipients, though iPSC-MSCs alone was inefficient in preventing rejection [4]. We also found that production of interleukin-2 and interferon-γ was reduced, which indicated iPSC-MSCs + Rapa treatment reduces Th1 inflammatory cytokines and may modulate T-cell phenotypes towards Th1 suppression. However, the iPSC-MSCs modulated T-cell phenotypes towards Th2 suppression in allergic rhinitis patients and animal models [2, 3]. These results indicate that iPSC-MSCs maybe exerts different effects and activities in different pathological conditions. It allows the iPSC-MSCs to rectify the imbalance of the immune responses in different environments. Previous studies have verified that adult MSCs alone, or combined with immunosuppressive drugs, induce allograft immune tolerance through Treg induction in vivo. Berman et al. first reported that infusions of donor or third-party MSCs prolonged islet function, which was associated with increased numbers of Tregs in peripheral blood [5]. We speculated that iPSC-MSCs exert the therapeutic effect possibly through the induction of Tregs, acting like adult MSCs. Since TGF-β is the perpetrator of immune suppression via regulatory T cells [6], we examined TGF-β expression in the islet grafts and sera of the recipient mice. The results showed that iPSC-MSCs + Rapa treatment increased sera TGF-β concentrations, and graft TGF-β mRNA levels, compared with Rapa treatment. Flow cytometry results also showed that the number of T regulatory cells was increased in spleen and lymph nodes in the iPSC-MSCs+ Rapa group compared with Rapa group. These results support our hypothesis. In addition to 2,3-dioxygenase, prostaglandin-E2, nitric oxide, TGF-β, and hepatocyte growth factor, IL-10 has been reported to induce MSC-mediated immunosuppressive effects. IL-10 induced by CD11b(+) cells and IL-10-activated regulatory T cells played important roles in immune modulation of mesenchymal stem cells in rat islet allografts [7]. In our research, iPSC-MSCs alone or in the combination with Rapa increased IL-10 secretion in sera, and IL-10 mRNA levels in the graft, whereas Rapa alone did not. Further research is still required to determine whether IL-10 mediates the immunosuppressive effect of iPSC-MSCs + Rapa on T cells. In addition, transwell separation significantly weakened the immunosuppressive effects of iPSC-MSCs on the proliferation of Con A-treated splenic T cells, which revealed that the combined treatment exerts its immunosuppressive effects though cell-cell contact and the regulation of cytokines production. Anti-aging and anti-cancer benefits of low-dose rapamycin were recently discussed [8]. The synergistic immunomodulatory effects of iPSC-MSCs and lowdose Rapa in islet transplantation suggest a promising strategy for inducing immune tolerance, not only in allogeneic islets transplantation, but also in other solid organ transplantation. There may be differences in immunosuppressive effects and mechanisms between iPSC-MSCs and MSCs from other sources. And the origin of the cell sources and the long-term effects of iPSC-MSCs also need to be investigated.

We investigated the acceptability of early anti-retroviral therapy (ART) among HIV-infected people in Anhui Province, China. A cross-sectional study was conducted in 11 convenience selected cities of Anhui Province from September 2012 to December 2013. Study participants were convenience recruited from local Centers for Disease Control and Prevention when they attended for CD4(+) cell counts testing and HIV counselling. Answers to questionnaires were obtained through face-to-face structured interviews. Factors influencing the acceptability of early ART were identified by multiple logistic regression analysis. A total of 287 HIV-infected people met the criteria and completed the survey. The acceptability of early ART was 65.2%. The results of multiple logistic regression analysis indicated that the acceptability of early ART was associated with the following factors: CD4(+) T cell count (above 750 cells/µL vs. 350 cells/µL to 550 cells/µL: OR = 0.144, P0.001), years of HIV diagnosis confirmation (1 year to 5 years vs.1 year: OR = 0.418, P = 0.005; above 5 years vs.1 year: OR = 0.160, P0.001), whether had sexual behaviour after HIV diagnosis confirmation (yes vs. no: OR = 2.342, P = 0.005) and the awareness of two early ART-related questions (OR = 4.101, P = 0.015; OR = 3.294, P0.001). In summary, the present study showed that most HIV-infected people can accept early ART. Early ART interest in Anhui HIV-infected population was high. The awareness of early ART-related knowledge in HIV-infected population was low and should be improved to achieve higher acceptability and keep adherence to early ART for HIV prevention.

The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and risk of acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the precise association in 23 studies identified by a search of PubMed and several other databases, up to December 2013. Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publication bias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 but not GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01, 95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1 null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors for acute leukemia. Further well-designed studies are needed to confirm our findings.

The goal of the present study was to determine the disparities in prevalence and risk factors of loneliness between rural empty nest and non-empty nest older adults in Chizhou, China.A sample of 730 participants (381 empty nest older adults and 349 non-empty nest older adults) were surveyed using the University of California at Los Angeles-Loneliness Scale, the 30-item Geriatric Depression Scale (GDS-30), the Pittsburgh Sleep Quality Index, the Social Support Rate Scale, the Perceived Social Support from Family Scale and the World Health Organization Quality of Life questionnaire abbreviated version.The present study showed that the mean level of loneliness did significantly differ between empty nest older adults and non-empty nest older adults (41.52 ± 6.98 vs 39.46 ± 7.38). Empty nesters had significantly higher GDS scores; by contrast, they received lower objective, subjective and family support. Family support, objective support and social interaction were associated significantly with loneliness, which was more pronounced in empty nest older adults, excluding subjective support and psychological domain. The GDS scores (β = 0.237, P 0.001) and age (β = -0.114, P = 0.002) showed stronger significant associations with loneliness in empty nest older adults.Loneliness obviously prevails among empty nest older adults than non-empty nest older adults. Depressive symptoms showed a stronger risk of empty nest older adults being lonely. Family support was suggested as a protective factor for loneliness in both groups. These findings should be considered when developing intervention strategies to reduce loneliness.

MicroRNA-183 (miR-183) family is proposed as promising biomarkers for early cancer detection and accurate prognosis as well as targets for more efficient treatment. The results of their expression feature in cancer tissues are inconsistent and controversy still exists in identifying them as new biomarkers of cancers. Therefore, to systemically evaluate the most frequently reported cancers in which miR-183 family members were up- or down-regulated is critical for further investigation on physiological impact of its aberrant regulation in specific cancers. The published studies that compared the level of miR-183 family expression in cancer tissues with those in noncancerous tissues were reviewed by the meta-analysis with a vote-counting strategy. Among the 49 included studies, a total of 18 cancers were reported, with 11 cancers reported in at least two studies. In the panel of miR-183 family members' expression analysis, colorectal cancer and prostate cancer ranked at the top among consistently reported cancer types with up-regulated feature. Bladder cancer, lung cancer and hepatocellular carcinoma were the third most frequently reported cancer types with significant over-expression of miR-96, miR-182 and miR-183 respectively. Breast cancer and gastric cancer were presented with inconsistent regulations and the members of this family had their own distinct regulated features in other different cancers. MiR-183 family, either individually or as a cluster, may be useful prognostic markers and/or therapeutic targets in several cancers. Further studies and repeat efforts are still required to determine the role of miR-183 family in various cancer progressions.

Hepcidin plays a central role in iron homeostasis, which is regulated by iron stores, the rate of erythropoiesis, inflammation, and hypoxia. Aberrant expression of hepcidin was found in many diseases, however, there is scant information on hepcidin expression in acute leukemia (AL).32 patients with AL which diagnosis according to FAB criteria were studied. Serum hepcidin levels, erythropoietin (EPO), interleukin-6 (IL-6), hematological parameters, intracellular and extracellular iron store were evaluated.Hepcidin was elevated significantly with increased iron storage in patients at onset of AL when erythropoiesis was depressed by blast cells, then decreased significantly with AL remission, while soluble transferrin receptor (sTfR) concentration was elevated. Negative correlations were found between serum hepcidin and erythropoietic markers including RBC, Hb, Ret and sTfR. Positive correlations were shown between hepcidin and ferritin, between hepcidin and ratio of sideroblasts, as well as between hepcidin and IL-6.Hepcidin production was regulated by iron stores, inflammation and erythropoietic activity in AL patients. Erythropoietic activity may play the main role among the regulators of hepcidin expresssion.

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

To further enhance anticancer effect of Shepherdin and overcome limitation of peptide therapy, recombinant adeno-associated virus (rAAV) was constructed with following strategies: therapeutic peptide secretory expression and adeno-associated virus gene transfer system. MTT assay and flow cytometric analysis revealed that rAAV harboring fusion gene NT4-Ant-Shepherdin significantly suppressed A549 cell growth in a time-dependent manner and induced apoptosis. In the infected A549 cells, survivin expression level decreased strongly while Caspase-3/7 activities increased significantly. These results indicated that rAAV harboring fusion gene NT4-Ant-Shepherdin may be a novel strategy in lung cancer peptide therapy.