Objective To study the relations among phlegm turbidity, blood stasis syndromes, Interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in simple hypertension patients and those complicated with abnormal blood fat and/or diabetes.Methods Totally 319 cases of hypertension collected were divided into the group with simple hypertension (simple group, 98 cases) and the group with hypertension complicated with abnormal blood fat and/or diabetes (complicated group, 221 cases). The patients were classified according to the 4 different syndromes, i.e., phlegm turbidity, blood stasis, phlegm turbidity plus blood stasis, and not phlegm turbidity not blood stasis. ELISA was used to measure serum IL-6 content, and latex enhancement immune turbidimetry was applied to determine hs-CRP content.Results The contents of IL-6 and hs-CRP of the two groups were not significantly different. The content of hs-CRP of both groups in the 4 syndromes was not significantly different. In the simple group, the content of IL-6 in the 4 syndromes was not significantly different either. In the complicated group, the content of IL-6 in the syndrome of phlegm turbidity plus blood stasis was significantly higher than in other syndromes (P

Objective Purpose understanding the prevalence of diabetes(DM) of Xuzhou mine workers and impacts on the incidence of risk factors, and discussing the prevention and treatment.Methods From November 2007 to March 2008,1180 Xuzhou mine workers were determinated by height,weight,abdominal circumference,blood pressure,fasting plasma glucose and lipid four(including triglycerides ,total cholesterol,low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), OGTT test.Results DM prevalence rate is 5.25 percent,more men than women;prevalence rate under 40 years old is lower,the prevalence rate from 40 to 50 year-old began to increase, to the top of 50-year-old.Overweight and obesity people took the most part.Conclusion DM is a common diseases among Xuzhou mining area in-service workers with high rates of prevalence,it connected with age,family history, occupation,body mass index(BMI),etc.

Protamines are a group of highly basic proteins first discovered in spermatozoon that allow for denser packaging of DNA than histones and will result in down-regulation of gene transcription[1].It is well recognized that the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) encodes P6.9,a protamine-like protein that forms the viral subnucleosome through binding to the viral genome[29].Previous research demonstrates that P6.9 is essential for viral nucleocapsid assembly,while it has no influence on viral genome replication[31].In the present study,the role of P6.9 in viral gene transcription regulation is characterized.In contrast to protamines or other protamine-like proteins that usually down-regulate gene transcription,P6.9 appears to up-regulate viral gene transcription at 12-24 hours post infection (hpi),whereas it is non-essential for the basal level of viral gene transcription.Fluorescence microscopy reveals the P6.9's co-localization with DNA is temporally and spatially synchronized with P6.9's impact on viral gene transcription,indicating the P6.9-DNA association contributes to transcription regulation.Chromatin fractionation assay further reveals an unexpected co-existence of P6.9 and host RNA polymerase Ⅱ in the same transcriptionally active chromatin fraction at 24 hpi,which may probably contribute to viral gene transcription up-regulation in the late infection phase.

The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle.In the present study using a Huh7 cell line Con1 with an HCV replicon,we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-α signalling.Epithelial growth factor (EGF) was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells.It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site.Consistently,a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfection assays.Thus,the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication.In addition,cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the modulation of HCV replication since roscovitine,an inhibitor of CDKs had a similar effect to that of U0126.Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels.Further,the replication of HCV replicon in Conl cells was inhibited by IFN-α.The inhibitory effect of IFN-α could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs.It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes.

Objective:To explore the effects of online character strengths intervention on the distress-related and self-management ability of young and middle-aged patients with type 2 diabetes. To provide reference for improving the physical and mental health of patients.Methods:Ninety-two young and middle-aged patients with type 2 diabetes admitted to the Second Affiliated Hospital of Xuzhou University of Medicine from July 2021 to July 2022 were selected and divided into intervention group and control group with 46 cases in each group by random number table method. The control group was given routine care, and the intervention group was given online character strengths intervention for 8 weeks. Diabetes-related distress Questionnaire (DDS) and Diabetes Self-Care Scale (DSCS) were used to evaluate the effects of the two groups of patients before intervention, immediately after intervention and 1 month after intervention.Results:The total DDS scores of the control group were (2.18 ± 0.70) and (2.01 ± 0.65) when the moment and 1 month after intervention, while the scores in the intervention group were (1.74 ± 0.47) and (1.18 ± 0.17), the differences were significant ( t = 3.13, 8.34, both P<0.05). The total DSCS scores of the control group were (72.25 ± 11.55) and (73.12 ± 10.72) when the moment and 1 month after intervention, while the scores in the intervention group were (85.95 ± 5.91) and (85.24 ± 5.21), the differences were significant ( t = 10.13, 2.10, both P<0.05). Conclusions:Online character strengths intervention can help alleviate the distress associated with young and middle-aged patients with type 2 diabetes and improve the level of self-management.

Objective By using mouse orthotopic lung transplant model, we investigated the immune mechanisms of an-ti-CD3 induced lung allograft protection .Our study intends to further dissect the features of lung transplant immunology and to provide a novel therapeutic insight for the clinical application of anti-CD3 mAbs after lung transplantation.Methods Murine orthotopic allogeneic lung transplants were performed in C57BL/6 wild type(WT) mice using major histocompatibility complex (MHC) fully mismatched BALB/c donors.Syngeneic transplants were also performed in WT C57BL/6 mice using C57BL/6 donors.For immunosuppressive therapy, allograft recipients received 50g dose of anti-CD3 by intraperitoneal injection on days 2, 3, 4, 5, 6 and 9 post-operation(n=4).At day 10, histopathologic characteristics and rejection status of the pulmonary grafts were assessed.The severity of acute rejection was graded by the pathological score , and T cell and neutrophil infiltration in the pulmonary grafts was evaluated by immunohistochemical(IHC) staining for CD3 and myeloperoxidase(MPO) respective-ly.Real-time RT-PCR was performed for FoxP3, IL-17A and IFN-γexpression in the pulmonary grafts.The percentage of FoxP3+Treg in total CD4+T lymphocytes from the recipient spleens was analyzed by FACS.Results 10 days after transplan-tation, histopathologic examination demonstrated that there is no apparent acute rejection observed in the pulmonary isografts , whereas allografts from untreated recipients have marked inflammatory cell infiltration and pulmonary parenchyma lesion .IHC staining for CD3 and MPO showed that the allograft-infiltrating cells of perivascular layers are mainly T lymphocytes , and the cells around the small airways are mostly neutrophils .Anti-CD3 treatment significantly alleviated the acute rejection of pulmo-nary allografts, when compared with the untreated group.Real-time RT-PCR showed that the expression levels of IL-17A and IFN-γin allografts were markedly elevated compared to those in isografts, and anti-CD3 increased the expression of FoxP3, and reduced the expression of IL-17A and IFN-γin the pulmonary allografts.FACS analysis of splenocytes showed that the percent-age of Treg in total CD4+T lymphocytes increased significantly in the anti-CD3 treated allograft recipients, as compared with the isograft and untreated allograft recipients.Conclusion Anti-CD3 mAbs may alleviate acute rejection of the pulmonary al-lografts by promoting FoxP3 expression and Treg development.

AIM: To investigate the polymorphism distribution of lipid and drug metabolism-related genes of SLCO1B1 and ApoE in patients with cardiovascular disease of Han nationality in Anhui province, and to evaluate the benefit-risk ratio of individual use of statins. METHODS: PCR fluorescence probe technique was used to detect the genetic polymorphism of rs2306283 (388A>G) and rs4149056 (521T>C) of SLCO1B1 as well as rs429358 (388 T>C) and rs7412 (526C>T) of ApoE in 736 individuals diagnosed with cardiovascular diseases in the inpatient department of the Second People's Hospital of Hefei from January 2019 to August 2020 were included. The distribution characteristics of SLCO1B1 and ApoE genotypes were analyzed according to the gender of the subjects, and the results of genetic polymorphism were compared with the data of cardiovascular disease patients in other areas of China. RESULTS: Six genotypes of SLCO1B1 had been detected. They were *1a/*1a (6.11%), *1a/*1b (29.08%), *1b/*1b (44.57%), *1a/*15 (4.08%), *1b/*15 (15.49%) and *15/*15 (0.68%), while *1a/*5, *5/*5 and *5/*15 had not been detected. Six genotypes of ApoE had been detected. They were E2/E2 (0.41%), E2/E3 (11.96%), E2/E4 (1.09%), E3/E3 (67.66%), E3/E4 (17.93%) and E4/E4 (0.95%). The frequency distribution of genetic polymorphism of these two genes satisfied the Hardy-Weinberg genetic equilibrium, which was representative of the population. In this study, the proportion of people with SLCO1B1 normal myopathy risk was the highest, accounting for 79.76%; SLCO1B1 had a lower proportion of people with moderate myopathy risk and high myopathy risk were 19.57% and 0.68%, respectively. The reduced risk, normal risk and increased risk phenotypes of ApoE were respectively 12.37%, 68.75% and 18.88%. There was no statistically significant difference in SLCO1B1 and ApoE genotypes beween gender. Compared with patients with cardiovascular disease in Southern China area, the distribution of ApoE genetic polymorphism was significantly different in Anhui. CONCLUSION: The SLCO1B1 and ApoE genetic polymorphism of 736 patients with cardiovascular diseases in Anhui were mainly normal myopathy risk types with higher dose tolerance of statins as well as popular genotypes that were sensitive to statins, and the application of statins has a lower risk of myopathy and a good effect on lipid reduction. The polymorphism of the two genes was not affected by gender, but the distribution phenotypes of ApoE might be different in regional characteristics. The detection of SLCO1B1 and ApoE genetic polymorphism is significant for evaluation of benefit-risk ratios, thereby guiding statins clinical treatment.

The secondary structures of hepatitis C virus (HCV) RNA and the cellular proteins that bind to them are important for modulating both translation and RNA replication. However, the sets of RNA-binding proteins involved in the regulation of HCV translation, replication and encapsidation remain unknown. Here, we identified RNA binding motif protein 24 (RBM24) as a host factor participated in HCV translation and replication. Knockdown of RBM24 reduced HCV propagation in Huh7.5.1 cells. An enhanced translation and delayed RNA synthesis during the early phase of infection was observed in RBM24 silencing cells. However, both overexpression of RBM24 and recombinant human RBM24 protein suppressed HCV IRES-mediated translation. Further analysis revealed that the assembly of the 80S ribosome on the HCV IRES was interrupted by RBM24 protein through binding to the 5'-UTR. RBM24 could also interact with HCV Core and enhance the interaction of Core and 5'-UTR, which suppresses the expression of HCV. Moreover, RBM24 enhanced the interaction between the 5'- and 3'-UTRs in the HCV genome, which probably explained its requirement in HCV genome replication. Therefore, RBM24 is a novel host factor involved in HCV replication and may function at the switch from translation to replication.
Cells, Cultured ; Hepacivirus ; genetics ; growth & development ; metabolism ; Humans ; Protein Biosynthesis ; RNA-Binding Proteins ; metabolism ; Virus Replication ; genetics

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*