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Hoping to find genomic clues linked to COVID-19 and end the pandemic has driven scientists tremendous efforts to try all kinds of research. Signs of progress have been achieved but are still limited. This paper intends to prove the existence of at least three genomic signature patterns and at least seven subtypes of COVID-19 driven by five critical genes (the smallest subset of genes). These signatures and subtypes provide crucial genomic information in COVID-19 diagnosis (including ICU patients), research focuses, and treatment methods. Unlike existing approaches focused on gene fold-changes and pathways, gene-gene nonlinear and competing interactions are the driving forces in finding the signature patterns and subtypes. Furthermore, the method leads to 100% accuracy, which shows biological and mathematical equivalences between COVID-19 status and the signature patterns and a methodological advantage over other existing methods that cannot lead to 100% accuracy. As a result, as new biomarkers, the new findings can be much more informative than other findings for interpreting biological mechanisms, developing the second (third) generation of vaccines, antiviral drugs, and treatment methods, and eventually bringing new hopes to an end of the pandemic.
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Genes functionally associated with SARS-CoV-2 infection and genes functionally related to COVID-19 disease can be different, whose distinction will become the first essential step for successfully fighting against the COVID-19 pandemic. Unfortunately, this first step has not been completed in all biological and medical research. Using a newly developed maxcompeting logistic classifier, two genes, ATP6V1B2 and IFI27, stand out to be critical in transcriptional response to SARS-CoV-2 infection with differential expressions derived from NP/OP swab PCR. This finding is evidenced by combining these two genes with one another gene in predicting disease status to achieve better-indicating accuracy than existing classifiers with the same number of genes. In addition, combining these two genes with three other genes to form a five-gene classifier outperforms existing classifiers with ten or more genes. These two genes can be critical in fighting against the COVID-19 pandemic as a new focus and direction with their exceptional predicting accuracy. Comparing the functional effects of these genes with a five-gene classifier with 100% accuracy identified and tested from blood samples in our earlier work, genes and their transcriptional response and functional effects to SARS-CoV-2 infection and genes and their functional signature patterns to COVID-19 antibody are significantly different, which can be interpreted as the former is the point of a phenomenon, and the latter is the essence of the disease. We will use a total of fourteen cohort studies (including breakthrough infections and omicron variants) with 1481 samples to justify our results. Such significant findings can help explore the causal and pathological clue between SARS-CoV-2 infection and COVID-19 disease and fight against the disease with more targeted genes, vaccines, antiviral drugs, and therapies.
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Objective To investigate the effect of thyroid stimulating hormone (TSH) on the expression of endothelial nitric oxide synthase (eNOS) and its mechanism in human microvascular endothelial cells (HMEC-1) in vitro culture.Methods Different concentrations of TSH (0,10,50 mIU/ml) were used to intervene HMEC-1.The expression of eNOS mRNA was detected with quantitative polymerase chain reaction (qPCR) method.The protein expressions of eNOS,phosphorylated protein kinase B (p-AKT),protein kinase B (AKT),phosphorylated extracellular signal-regulated kinase (P-ERK),and extracellular signal-regulated kinase (ERK) were determined with Western Blot.Results (1) The expression level of eNOS was significantly decreased by TSH in dose-dependent manner (P ＜ 0.05).(2) TSH could promote the phosphorylation of AKT and ERK (P ＜ 0.05).Conclusions Thyroid-stimulating hormone may inhibit the expression of nitric oxide synthase in human microvascular endothelial cells by activating AKT and ERK signaling pathways.
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Objective To investigate the relationship between iodine nutritional status and thyroid hormone levels,and to provide a guideline for monitoring iodine nutrition and thyroid function.Methods A crosssectional survey was performed by randomly selecting 341 samples (health pregnant women with a first child) from the Second People's Hospital of Guiyang,Bihai Community Medical Center and Jinhuayuan Community Center from October 2015 to September 2016.Levels of serum hormones and antibodies relative to throid of pregnant women in Guanshan Lake District of Guiyang at different pregnant times,which included throid stimulating hormone (TSH),free three triiodothyronine (FT3),free thyroxine (FT4),thyroid peroxidase antibody (TPOAb),and thyroglobulin antibody (TgAb),were measured by the electrochemical luminescence method,and urinary iodine levels were measured by heat digestion.Results The median urinary iodine of pregnant women at early,middle and late stages (T1,T2 and T3 stages) were 191.8,198.9 and 214.5 μg/L,respectively.FT3 increased first and then decreased during pregnancy.Levels of FT3 in the T2 stage were significandy higher than those in T1 and T3 stages (FT3 medians at the three stages were 4.49,4.83 and 4.57 pmol/L),and the differences were statistically significant (P ＜ 0.05).FT4 levels decreased during pregnancy (FT4 medians at the three stages were 16.32,14.65 and 13.22 pmol/L),and the differences among the three groups were statistically significant (H =67.517,P ＜ 0.01).Statistically significant differences were not found in the TSH levels among the three groups ~SH medians at the three stages were 2.05,2.01 and 2.39 mU/L,H =1.297,P ＞ 0.05).The medians of TPOAb and TgAb during T2 stage (9.60 and 19.02 U/ml) were significantly lower than those of other groups (18.92 and 24.75 U/ml at stage T1,and 13.46 and 22.06 U/ml at stage T3),and the differences were statistically significant (P ＜ 0.05).TSH levels were consistent with urinary iodine levels.TSH levels in the excessive iodine group (urine iodine:250 ～ 499 μg/L,2.54 mU/L) were significantly higher than those in the adequate iodine group (urine iodine:150 ～ 249 μg/L,1.97 mU/L) and deficient iodine group (urine iodine:＜ 150 μg/L,1.91 mU/L),and the differences were statistically significant (P ＜ 0.05).No correlations were found between levels of FT3,FT4,TPOAb,TgAb and levels of the urinary iodine.There was a significant positive correlation between urinary iodine levels and TSH levels (rs =0.180,P ＜ 0.01).The incidence of abnormal thyroid function in pregnant women was 29.33％ (100/341),which was composed of clinical hypothyroidism (accounting for 0.88％,3/341),subclinical hypothyroidism (accounting for 25.51％,87/341),low T4 level (accounting for 1.76％,6/341),clinical hyperthyroidism (accounting for 0.59％,2/341),subclinical hyperthyroidism (accounting for 0.59％,2/341),and TPOAb positive and TgAb positive (accounting for 12.61％,43/341).These abnormalities occurred mainly in the T1 and T3 stages.The prevalence of subclinical hypothyroidism increased with increasing of urinary iodine level,and the difference was statistically significant (x2 =11.269,P ＜ 0.05).Conclusion There is a positive correlation between pregnancy iodine nutritional status and its TSH level,so it is important to monitor the level of urinary iodine during pregnancy and to screen the thyroid function and antibodies in the early and middle time of pregnancy.
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Objective To investigate the changes of serum thyroid peroxidase(TPOAb)and thyroglobulin antibody(TGAb)and their relationship with thyroid function in pregnant women during different gestation period Methods Totally 341 cases of primiparae were selected from October 2015 to September 2016 and levels of se-rum thyrotropin(TSH),free triiodothyronine(FT3),free thyroxine(FT4),thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody(TgAb)were measured by electrochemiluminescence. Results The prevalence of thy-roid dysfunction and positive serum thyroid autoantibodies were 13.2%and 12.61%respectively,which mainly oc-curred in early and middle pregnancy. Thyroid dysfunction in subjects included hypothyroidism(0.59%),subclini-cal hypothyroidism(7.92%),low T4 hyperlipidemia(3.23%),hyperthyroidism(0.88%)and subclinical hyper-thyroidism(0.59%). The positive rate of TPOAb was significantly higher than that of TgAb(10.85% vs. 4.99%, P<0.01). The positive rate of TPOAb in women with thyroid disfunction was significantly higher than that in those with normal thyroid function(44.44%vs. 5.74%,P<0.01). TSH level of TPOAb positive subjects was higher than that of TPOAb negative ones(P<0.05,P<0.01);TSH level of TPOAb positive subjects with thyroid dysfunction were significantly higher than those of TPOAb negative subjects and TPOAb positive pregnant women but with nor-mal thyroid function(P < 0.01). The hypothyroidism prevalence rate of TPOAb positive subjects was significantly higher than that of TPOAb negative subjects in early and middle stage of pregnancy (P < 0.01). The prevalence rates of subclinical hypothyroidism ,low T4 hyperlipidemia and clinical hypothyroidism were significantly higher in TPOAb positive pregnant women(29.17%,20.83% and 8.33%)than those in TPOAb negative pregnant women (P < 0.01). Conclusions Thyroid dysfunction is closely related to positive status of TPOAb and TgAb in pregnancy,which could influence the outcome of pregnancy and the development of offspring. Since levels of TSH, FT3 and FT4 could not fully reveal thyroid function ,it is necessary to monitor the status of TPOAb and TgAb as early as possible for the early diagnosis and treatment of thyroid disease in pregnancy.
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Objective To investigate the changes of serum thyroid peroxidase(TPOAb)and thyroglobulin antibody(TGAb)and their relationship with thyroid function in pregnant women during different gestation period Methods Totally 341 cases of primiparae were selected from October 2015 to September 2016 and levels of se-rum thyrotropin(TSH),free triiodothyronine(FT3),free thyroxine(FT4),thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody(TgAb)were measured by electrochemiluminescence. Results The prevalence of thy-roid dysfunction and positive serum thyroid autoantibodies were 13.2%and 12.61%respectively,which mainly oc-curred in early and middle pregnancy. Thyroid dysfunction in subjects included hypothyroidism(0.59%),subclini-cal hypothyroidism(7.92%),low T4 hyperlipidemia(3.23%),hyperthyroidism(0.88%)and subclinical hyper-thyroidism(0.59%). The positive rate of TPOAb was significantly higher than that of TgAb(10.85% vs. 4.99%, P<0.01). The positive rate of TPOAb in women with thyroid disfunction was significantly higher than that in those with normal thyroid function(44.44%vs. 5.74%,P<0.01). TSH level of TPOAb positive subjects was higher than that of TPOAb negative ones(P<0.05,P<0.01);TSH level of TPOAb positive subjects with thyroid dysfunction were significantly higher than those of TPOAb negative subjects and TPOAb positive pregnant women but with nor-mal thyroid function(P < 0.01). The hypothyroidism prevalence rate of TPOAb positive subjects was significantly higher than that of TPOAb negative subjects in early and middle stage of pregnancy (P < 0.01). The prevalence rates of subclinical hypothyroidism ,low T4 hyperlipidemia and clinical hypothyroidism were significantly higher in TPOAb positive pregnant women(29.17%,20.83% and 8.33%)than those in TPOAb negative pregnant women (P < 0.01). Conclusions Thyroid dysfunction is closely related to positive status of TPOAb and TgAb in pregnancy,which could influence the outcome of pregnancy and the development of offspring. Since levels of TSH, FT3 and FT4 could not fully reveal thyroid function ,it is necessary to monitor the status of TPOAb and TgAb as early as possible for the early diagnosis and treatment of thyroid disease in pregnancy.
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Objective:To explore the role CD4+CD45RO+memory T cells in the pathogenesis of Hashimoto's thyroiditis (HT) by detecting the percentages of CD4+CD45RO+ memory T cells in peripheral blood mononuclear cells in peripheral blood of newly diagnosed HT patients. Methods:53HT patients and 43 matched healthy controls (HC) were included in this study. According to the thyroid functions,HT patients were divided into euthyroid subset(HT-A,n =15) ,subclinical hypothyroidism(HT-B,n=14) and overt hypothyroidism subset (HT-C,n=24). The percentages of CD4+CD45RO+memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,and thyroid functions,and the titers of thyroid-specific autoantibodies (TPOAb,TgAb) were respectively detected by flow cytometry,ELISA,and ECLIA. Results:The percentages of CD4+CD45RO+ memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,the titers of TPOAb,TgAb were all significantly higher than that in HC(P<0. 01). Bivariate correlation revealed that the percentages of CD4+CD45RO+ memory T cells positively correlated with the level of serum IFN-γ,TPOAb and TgAb(P<0. 01,P=0. 015,P<0. 01) in HT patients. Conclusion:The significant increase of CD4+CD45RO+memory T cells in peripheral blood of patients with HT suggested a role of CD4+CD45RO+ memory T cells in the pathogenesis of this disease.
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Objective To evaluate the effect of spleno-left adrenal vein shunt for the treatment of portal hypertensive upper GI bleeding caused by portal vein cavernous transformation in children.Methods Spleno-left adrenal vein shunt was performed in 8 children with portal hypertension due to cavernous transformation.The clinical data was reviewed.Results Portal vein pressure decreased significantly from (30±11)mm Hg to(22±7) mm Hg after shunt.There was no mortality perioperatively and during the follow-up.There were no recurrent hemorrhage nor hepatic encephalopathy occurring in the follow-up and all the children have normal intelligence and normal liver function though blood ammonia level increased significantly from(18±7)μmol/L to (60±17)μmol/L in 4 cases.In 7 cases in which preoperative whole blood cell count significantly decreased,the postoperative WBC,RBC,Hb and PLT was (7.64 ±4.46)×10~9/L,(4.54±0.97)×10~(12)/L,(133±5) g/L and (355.40±107.36)×10~9/L respectively (all P ＜0.05).In one case suffering from preoperative low PLT count the postop PLT reached 333×10~9/L,which was significantly higher than that preoperatively.Esophageal varices ameliorated in 6 cases.No stenosis of anastomotic stoma and thrombosis developed.Conclusion Spleno-left adrenal vein shunt is an effective procedure to treat portal vein cavernous transformation induced portal hypertension in children.
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Objectlve To explore the mechanism of the protection in high expression of HO-1 induced by CoPP on murine islet xenografts. Method An islet transplantation of a SD rat-to-C57 BL/6 mouse model was established.Mice were randomized into five groups i.e.control,CoPP-induction in vivo,CoPP+ZnPP in vivo.CoPP-induction in vitro and CoPP+ZnPP in vitro and the islet xenografts were transplanted into the subrenal capsule.Normoglycemia time was recorded and insulin-releasing test was performed.IL-10、TNF-α、IL-1β and INF-γ in serum and their cytokine mRNA and HO-1 in xenografts were measured by RT-PCR and Western-blotting.The pathological examination was done to observe the lymphocyte infiltration. Results There Was significant difference in the normoglycemia time between CoPP-induction in vivo and in vitro and other three groups.The results of insulin-releasing stimulated by low level glucose were identical among groups,but that of insulin-releasing stimulated by high-glucose in in vivo group were the hiishest as in CoPP-induction in vivo and in vitro and control group were 187.68 ±19.93、137.22±11.73,91.25±12.64 μIU·ml~(-1)·10islets~(-1)·45 min~(-1),(P<0.05).The IL-10 in serum in CoPP-induction in vivo and in vitro(in vivo:72.97±9.74 pg/ml;in vitro:70.84±3.56 pg/ml)was significantly hisher than other three groups(control:30.57±3.93 pg/ml;CoPP+ZnPP in vivo:39.78±3.00 pg/ml;CoPP+ZnPP in vitro:35.42±4.30 pg/ml).The expression tendency of IL-10 mRNA was similar to that of insulin secretion.There was no significant difieFence in TNF-α、IL-1β and INF-γ.The expression of HO-1 by PCR and Western-blot analysis in CoPP-induction in vivo and vitro was higher than other three groups.The pathological examination showed that fewer lymphocytes infiltrated into the islet xenografts from CoPP-treated in comparison with xenografts from other three groups. Conclusion HO-1 could improve the survival of islet xenograft:the induetion of HO-1 expression in vivo was much mole efficient than in vitro.The CoPP-induction could be related to immune modulation of IL-10.