Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective To screen the targets related to the metabolic enzymes involved in the cholesterol synthesis pathway that inhibits the polarization of macrophages towards M1 phenotype,and verify the intervention effects and underlying mechanisms in colorectal cancer cells.Methods Mouse colorectal cancer MC38 cells were divided into control group(si-NC)and experimental groups(the expression of enzymes in cholesterol synthesis pathway was interfered with siRNA for corresponding targets).RT-qPCR was used to detect the mRNA levels of corresponding targets in MC38 cells after transfection.After peritoneal macrophages were extracted from male C57BL/6 mice(6 weeks old,weighing 13～18 g),the macrophages were then treated with the conditioned media of MC38 cells transfected with different siRNAs for 48 h.RT-qPCR was employed to detect the mRNA levels of IL-1β,IL-6 and TNF-α in the macrophages so as to evaluate the effect of the culture media on the M1 polarization.MC38 cells were divided into control groups(OE-NC and sh-NC),farnesyl-diphosphate farnesyltransferase 1(FDFT1)overexpression group(OE-FDFT1)and FDFT1 knockdown group(sh-FDFT1).RT-qPCR was applied to detect the mRNA expression of FDFT1,and Western blotting was conducted to measure the protein level of FDFT1.C57BL/6 mice were subjected randomly to construct a subcutaneous tumor-bearing model and a model of intraperitoneal metastatic tumor(n=5)respectively.The growth of tumor mass was then measured.Flow cytometry was used to observe the proliferation and apoptosis of MC38 cells,and Trans well assay to detect migration ability of MC38 cells.Five C57BL/6 macrophage-depleted mice(established with injection of clodronate liposome suspension through tail vein)received intraperitoneal implantation to construct a metastasis model,and then the obtained tumor masses were then weighted.Results Compared with MC38 cells after si-NC transfection,the mRNA levels of corresponding targets in MC38 cells in the experimental groups were significantly reduced(P＜0.05).Significant increases were found in the mRNA levels of IL-1β,IL-6 and TNF-α of the macrophages with FDFT1 interference than the control cells(P＜0.05).There were no statistical differences in the proliferation,apoptosis and migration of MC38 cells in the control group(OE-NC and sh-NC)and the cells of the FDFT1 overexpression group and FDFT1 knockdown group(P＞0.05).In both the subcutaneous tumor-bearing model and the model of intraperitoneal metastatic tumor,the mass weight was significantly heavier in the OE-FDFT1 group than the OE-NC group(P＜0.01),and was notably smaller in the sh-FDFT1 group than the sh-NC group(P＜0.01).For the macrophage-depleted mouse tumor model,no remarkable change was observed in the tumor weight between the OE-FDFT1 group and the OE-NC group as well as the sh-FDFT1 group and the sh-NC group.Conclusion FDFT1,the metabolic enzyme in the cholesterol synthesis pathway of colorectal cancer tumor cells,is a potential target for tumor immunotherapy targeting macrophages,which promotes tumor progression by regulating macrophages.

Objective:To investigate genetic characteristics of human rhinovirus (HRV) in adult inpatients with pneumonia in autumn and winter in Bengbu, Anhui province, 2021.Methods:The pharyngeal swabs of inpatients with pneumonia in Bengbu were collected for the detection of 14 common respiratory pathogens by Real-time PCR during September to December 2021. VP4/VP2 coding regions of HRV positive samples were amplified by nested PCR and phylogenetic tree was constructed using MEGA7.0.Results:A total of 146 samples were collected from inpatients with pneumonia; 35.62% (52/146) samples were positive with at least one pathogen. The four viruses with high detection rate were HRV, adenovirus, human coronavirus OC43 and influenza B virus. HRV positive samples accounted for 44.23% (23/52) of the positive samples, among which 9 cases (39.13%, 9/23) co-infected with HRV. Phylogenetic analysis found that HRV infection were dominated by HRV-A and HRV-B groups. The analysis based on clinical syndrome found that the white blood cells count and the proportion neutrophils of patients with HRV co-infection were higher that of HRV single infection. The proportion of patients with hypertension, diabetes, mechanical ventilation and poor prognosis in the HRV co-infection group were higher than that of HRV single infection group ( P<0.05). Conclusions:HRV is the predominant pathogen among the adult inpatients with pneumonia in Bengbu. HRV-A and HRV-B groups are common. Patients accompanied by hypertension, diabetes were easily co-infected with HRV. Patients coinfeted with HRV are more likely to be mechanical ventilation and poor prognosis.

Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction (MI). MicroRNA-146b (miR-146b) is an active regulator of immunomodulation, but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following MI remain largely unknown. Herein, miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients. Gain- and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells. Overexpression of miR-146b-5p activated fibroblast proliferation, migration, and fibroblast-to-myofibroblast transition, impaired endothelial cell function and stress survival, and disturbed macrophage paracrine signaling. Interestingly, the opposite effects were observed when miR-146b-5p expression was inhibited. Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1 (IRAK1) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death, and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine MI models. Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following MI.

Objective To determine the clinical characteristics in elderly patients with Guillain-Barré syndrome ( GBS) and explore the relationship between glucose metabolism and severity and prognosis of disease. Methods Records of patients with GBS admitted between January 2004 and February 2017 from Affiliated Hospital of Jiangsu University were evaluated, including antecedent infection, initial symp-toms, cranial nerve palsy, subgroup analysis, Hughes score and Medical Research Council ( MRC) score at nadir and when discharged. Results The incidence of ocular palsy (6. 4％ vs 27. 0％, P=0. 02) and of facial palsy (18. 8％ vs 45. 8％, P =0. 016 ) were both lower in older group, compared to non-elderly group. MRC score at nadir (32 vs 44, P=0. 020), rate of severe type (80. 6％ vs 47. 9％, P=0. 004) and rate of poor prognosis when discharged (67. 7％ vs 29. 2％,P=0. 001) in elderly group were higher than non-elderly group. As to the distribution of subtype in these two groups, no significant difference was found (P=0. 691). Hyperglycemia wasn't prognostic factor of severe type (OR =0. 531,P =0. 321) or poor short-term prognosis (OR=0. 519,P=0. 261). Conclusions The clinical characteristics of elderly patients with GBS are distinct from non-elderly patients. Hyperglycemia wasn 't predictor of severe type or poor short-term prognosis of GBS.

Objective To observe the clinical efficacy of auricular point sticking with magnetic bead in treating insomnia in hepatocirrhosis patients. Method Ninety patients with hepatocirrhosis complicated with insomnia were randomized into a treatment group and a control group, 45 in each group. The treatment group was intervened by auricular point sticking with magnetic bead, while the control group was by auricular point sticking with medical adhesive tape. After successive 2-week treatments, the Insomnia Severity Index (ISI) and the Evaluation Criteria of Therapeutic Efficacy for Mental Disorders were observed for evaluating the treatment result. Result The ISI was significantly improved in the treatment group after intervention (P<0.05), and the improvement was significantly different from that in the control group (P<0.05). The total effective rate was 86.7% in the treatment group versus 60.0% in the control group, and the difference was statistically significant (P<0.01). Conclusion Auricular point sticking with magnetic bead is easy-to-operate and can produce a satisfactory efficacy in treating insomnia of hepatocirrhosis patients.

Objective To investigate the feasibility of centerline measurement method in estimating aortic diameter at the proximal landing zone in Stanford B type aortic dissection. Methods CT angiography materials of 30 patients with type B aortic dissection were randomly selected from the hospital database (24 males with a median age of 49.5 years), which were retrospectively analyzed with multiplanar reformation (MPR) and centerline technique by two experts in vascular radiology. Difference between two measurement techniques was analyzed by using mixed linear model, and the agreement of measurements between two readers as well as between two techniques were evaluated by Bland-Altman plots. Results The diameters measured with MPR method by two experts were (29.73±2.99) mm and (29.86±2.95) mm respectively, while the diameters measured with centerline measurement method by two experts were (29.66 ±2.81) mm and (29.71 ±2.91) mm respectively. No statistically significant differences in the diameter value existed between the two measurement methods, although the results determined by centerline measurement method were more stable. Conclusion In determining aortic diameter at the proximal landing zone in Stanford B type aortic dissection, the centerline analysis provides a checking method for MPR measurement.

Background: Chronic hepatitis C is one of the major causes of end-stage liver disease with a high incidence rate, amounting to a grave and serious problem of public health. Currently, interferon-based (with or without ribavirin) antiviral therapy has limited use due to its stringent indications, possible contraindications and side effects. Traditional Chinese medicine (TCM) may have advantages in the prevention and treatment of chronic hepatitis C and it is of significant value to discover the advantages. Through this research, a safe and effective treatment protocol of TCM or integrated TCM and Western medicine for chronic hepatitis C can be formed. To this end, during China's Eleventh Five-Year Plan, special research projects on acquired immune deficiency syndrome (AIDS), viral hepatitis and the other major infectious diseases were established. Our studies on chronic hepatitis C constitute one of the major special research topics. Methods and design: Clinical information of patients with chronic hepatitis C will be first collected in a large, multicenter epidemiological survey. Positive symptoms will be analyzed by rapid cluster analysis, principal constituent analysis and factor analysis, and syndrome types will be diagnosed based on expert advice. Concurrently, a large, multicenter, randomized, parallel-group prospective study will be launched based on evidence-based medical principles to evaluate the effects and safety of the treatment protocol for chronic hepatitis C. The evaluated indexes will include the normalization rate of liver function, virological improvement and quality of life improvement for the short-term efficacy and the incidence of liver cirrhosis and (or) primary liver cancer and mortality for the long-term efficacy. Discussion: This study will investigate the TCM syndrome differentiation norms and the syndrome distribution rules of chronic hepatitis C and evaluate the efficacy and safety of a treatment protocol for chronic hepatitis C based on TCM theory or combined treatment of TCM and Western medicine. The study results will be helpful to developing a TCM treatment program for chronic hepatitis C. Trial registration: The research program was registered in the Chinese Clinical Trial Registry in English and Chinese in January 2010. Registration number: ChiCTR-TRC-10000770.

Objective:To explore the relationship betwwen the different types of ischemic cerebrovascular disease andthe levels of plasma Homocystine(Hcy).Methods:The levels of plasma Hcy in 135 patients with ischemic cerebrovascular disease were measured by the fluorometric method.All the patients were divided into transient ischemic attack(TLA)group and atherothrombotic cerebral infarction(ACO group.The patients in both groups and the levels of plasma Hcy between the primary ACI and recurrent ACI were compared.Results:The levels of plasma Hcy in the ACI group(22.0±6.4 μmol/L)group were significantly higher than those in the TIA group(16.6±6.0 μmol/L)(P＜0.01),and the levels of plasma Hcy in the recurrent ACI group(23.0±5.5 5 μmol/L)were significantly higher than those in the primary group(19.6±5.9 μmol/L)(P＜0.01).There were rio significant differences between the two groups in age,sex,history of smoking.lipid,body mass index,as well as the prevalences of hypertension,diabetes mellitus and coronary heart disease.Conclusions:The increased level of plasma Hcy is closely associated with ACI.and it is a risk factor for recurrent stroke.