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AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
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ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction (MI). MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education, lifestyle adjustment, risk factors control, medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core, village/community physicians as the main executive body, and tertiary TCM hospital specialists as the leading body", for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys, various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate, and the secondary efficacy indicators included disease awareness-related indicators, lifestyle behavior-related indicators, cardiovascular risk factor-related indicators and Canadian cardiovascular society (CCS) cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% (59 cases) and 20.25% (49 cases), respectively, significantly lower than 36.08% (92 cases) and 53.72% (130 cases) before management (P<0.05). Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management (P>0.05), awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management (P<0.01), as well as the total score (P<0.01). In terms of daily life behaviors, the rates of salty diet, sweet diet and greasy diet were significantly lower than baseline, while the rate of moderate exercise was significantly higher (P<0.05 or P<0.01); the rates of ongoing smoking and vigorous exercise were not significantly changed (P>0.05). For cardiovascular risk factors, patients' total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, total depression assessment scale score, and total anxiety assessment scale score were significantly reduced after management (P<0.01). Systolic blood pressure and body mass index (BMI) were both higher after management (P<0.05 or P<0.01), and there was no statistically significant difference in diastolic blood pressure (P>0.05). In terms of the cardiovascular disease risk factors reaching the standard levels, the rate of LDL cholesterol <1.8 mmol/L significantly increased (P<0.01), while the rate of BMI <24 kg/m2 and the rate of systolic blood pressure <140 mmHg both decreased significantly (P<0.05 or P<0.01) from baseline; the diastolic blood pressure and rate of fasting glucose <7.0 mmol/L were not significantly changed (P>0.05). The patients' CCS cardiac function classification was significantly reduced (P<0.05). ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease, change poor lifestyle habits, reduce risk factors such as blood lipids and blood glucose, improve anxiety and depression, increase activity tolerance, and reduce their recurrence exacerbation and readmission rates, which is worthy of clinical promotion.
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Background/Aims@#Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. @*Methods@#LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. @*Results@#A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. @*Conclusions@#Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.
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ObjectiveTo investigate the expression and role of response gene to complement 32 (RGC32) in liver regeneration after partial hepatectomy (PH). MethodsA total of 42 male C57BL/6 mice, aged 10 weeks, were randomly divided into control group, postoperative day 1 group (1-d group), postoperative day 2 group (2-d group), postoperative day 4 group (4-d group), postoperative day 6 group (6-d group), postoperative day 8 group (8-d group), and postoperative day 10 group (10-d group), with 6 mice in each group. In the control group, the complete liver of the mice was resected for weighing and photography as the normal control group (sham group); further, the left and middle lobes of the liver were resected for weighing and photography as the surgical control group (0-day group); the sham group and the 0-day group shared the same group of mice. After successful modeling by PH, the mice were sacrificed on days 1, 2, 4, 6, 8, and 10 after surgery, and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes; serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to evaluate the changes in liver function; immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen (PCNA) and Ki67 and analyze the change in cell proliferation during liver regeneration; quantitatie real-time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration; EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data, comparison between multiple groups was made by analysis of variance, and further pairwise comparisons were conducted using the LSD-t test. The independent samples t-test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH, and the liver/body weight ratio rose to the peak from days 0 to 6, with significant differences between different time points (all P<0.05), while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration, with a significant difference between the portal vein region and the central vein region (all P<0.05). Compared with the sham group, the 1d group had significant increases in the serum levels of ALT and AST (all P<0.05), which gradually returned to the levels of the sham group on day 6 and day 2 after surgery, respectively (P>0.05). Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA- and Ki67-positive liver parenchymal cells after PH surgery, with the highest numbers of 86±5 and 89±5, respectively, on day 2, which then gradually decreased; however, there were gradual increases in the numbers of PCNA- and Ki67-positive nonparenchymal cells, with the peak numbers of 34±5 and 25±3, respectively, on day 6, which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased, and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression; however, the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells (R2=0.308 3, P=0.016 7), and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells (R2=0.808 6, P<0.000 1). Cell experiments showed that compared with the control group, the EdU-positive rate was reduced by 15.6% after RGC32 overexpression (P<0.01) and was increased by 19.2% after RGC32 knockdown (P<0.01). ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy, there are differences in the expression of RGC32 between nucleus and cytoplasm, and RGC32 in nucleus may inhibit hepatocyte proliferation.
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Objective:To explore the correlation between differential immune-related genes(DIRGs)and immune cells in the progression of atherosclerosis(AS)and general rule of Chinese medicine for intervening DIRGs.Methods:Firstly,GSE28829 data set was obtained from GEO database,and immune-related genes were downloaded from ImmPort database and MSigDB database.Secondly,differentially expressed genes between early AS plaques(EAP)and advanced AS plaques(AAP)of GSE28829 were screened by limma package,and their intersections with immune-related genes were known as DIRGs.clusterProfiler package was used to enrich the DIRGs.Protein interaction network of DIRGs was constructed and Hub genes were screened.Then,the infiltration patterns of 22 kinds of immune cells were analyzed by CIBERSORT to screen differential immune cells,and the correlation between them and Hub genes were analyzed by Pearson method.Finally,Coremine Medical database was used to predict Chinese herbs for in-tervening DIRGs,the property and flavor of Chinese herbs were collected.Results:Total 63 DIRGs were obtained,and 10 Hub genes(CD86,TLR2,TYROBP,CCR1,ITGB2,CCL2,CCL4,CSF1R,CXCR4,CTSS)were screened out.Enrichment analysis results showed that the molecular functions,biological processes and signaling pathways of DIRGs were closely related to immune regulation.Analysis of immune cell infiltration showed that proportions of regulatory T cells,activated dendritic cells and resting mast cells in EAP were increased.Proportions of memory B cells,γδ T cells,M0 macrophages and M2 macrophages were increased in AAP.Correla-tion analysis showed that CD86 was positively correlated with M2 macrophages in EAP.In AAP,CD86,CTSS,CXCR4,CSF1R,ITGB2 and TYROBP were positively correlated with M0 macrophages,while CCL4 and CCL2 were negatively correlated with resting mast cells.Results of frequency showed that Chinese herbs for intervening DIRGs mainly distributed to liver and lung meridians,and their property and taste were cold and bitter.Conclusion:This study found that in the progression of AS,10 DIRGs were the most important,and 7 kinds of immune cells were dysregulated,among which CD86,CTSS,CXCR4,CSF1R,ITGB2,TYROBP,CCL4 and CCL2 were correlated with resting mast cells,M0 and M1 macrophages.At the same time,immune mechanism of AS progression was closely related to liver meridian,lung meridian,bitter,sweet,cold and warm.The results can provide reference and ideas for Chinese herbs clinical prescription to treat AS and further exploratory the immunological mechanism of AS progression.
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Objective To explore the medication rules of clinical prescriptions of Chinese medicine in the treatment of heart failure with diuretic resistance based on data mining method.Methods Seven domestic and foreign databases,including CNKI and Wanfang,were searched for literature on Chinese medicine for heart failure with diuretic resistance from the establishment of the database to October 2021.Frequency analysis,association rule analysis and cluster analysis were used for statistical analysis.Results A total of 41 literatures were included,including 39 prescriptions.Yang deficiency and water retention were the main symptoms of the disease.A total of 72 single herbs were used,with a total of 438 times of use.There are 30 Chinese medicines with a frequency of more than 5 times,involving 9 efficacy categories,mainly tonic medicines,diuresis and dampness medicines,blood-activating and stasis-removing medicines,and interior-warming medicines.The association rule analysis yielded drug compatibility with Poria as the core,such as Atractylodis Macrocephalae Rhizoma→Poria and Cinnamomi Ramulus→Poria.Cluster analysis yielded six new formula combinations with efficacy in warming Yang,inducing diuresis,benefiting qi and invigorating Blood.Conclusion Heart failure with diuretic resistance is a syndrome of root vacuity and tip repletion,cold-heat complex,and the core pathogenesis is"deficiency","water"and"stasis".The treatment of this disease occurs by warming yang and excreting water,supplemented by replenishing qi and activating blood circulation.Poria with Atractylodis Macrocephalae Rhizoma and Cinnamomi Ramulus are commonly used combinations,and Zhen Wu Decoction is the basic formula for the treatment of this disease.
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Objective To explore the application value of serum cystatin C (Cys-C)and β2-micro-globulin (β2-MG)in the diagnosis and short-term efficacy evaluation of multiple myeloma (MM). Methods A total of 450 patients with MM admitted to Anqing Hospital of Chinese People's Liberation Army Navy and Jin-hua Central Hospital of Zhejiang Province from October 2016 to October 2018 were selected as subjects (MM group),according to the Durie-Salmon staging criteria,including 150 patients in stage Ⅰ,Ⅱ and Ⅲ. A total of 150 healthy subjects were selected as the control group. The levels of Cys-C and β2-MG in the serum of the subjects were determined. The differences of Cys-C and β2-MG levels between the two groups and the MM patients with different Durie-Salmon stages were compared. The differences of Cys-C and β2-MG levels between the patients with different short-term efficacy were compared. The receiver operating characteristic (ROC) curve was used to analyze the value of the two indicators in the evaluation of MM efficacy,and the correlation between Cys-C and β2-GM was analyzed. Logistic regression analysis was used to analyze the multiple factors affecting the clinical efficacy of MM patients. Results The levels of Cys-C and β2-MG in the serum of the patients with MM were (2. 11 ± 0. 78)mg/ L and (6. 07 ± 3. 08)g/ L respectively,and those in the control group were (0. 75 ± 0. 20)mg/ L and (1. 78 ± 0. 59)g/ L,with significant differences (t = 33. 848,P <0. 001;t = 28. 084,P < 0. 001). The Cys-C levels of Durie-Salmon stage Ⅰ,Ⅱ and Ⅲ patients were (0. 99 ± 0. 21)mg/ L,(1. 36 ± 0. 17)mg/ L and (3. 07 ± 1. 02)mg/ L respectively,and the difference was statistically significant (F = 44. 157,P < 0. 001). The β2-MG levels in the serum of patients with stage Ⅰ,Ⅱand Ⅲ were (2. 57 ± 0. 75)g/ L,(4. 66 ± 1. 43)g/ L,(8. 63 ± 2. 26)g/ L respectively,and the difference was statistically significant (F = 57. 285,P < 0. 001). In all the patients,338 patients were effective,accoun-ting for 75. 11%,and 112 patients were ineffective,accounting for 24. 89% . The levels of Cys-C and β2-MG in the serum of the effective MM patients were (1. 28 ± 0. 23)mg/ L and (2. 82 ± 0. 78)g/ L,and those of ineffective patients were (2. 97 ± 0. 77)mg/ L and (6. 22 ± 1. 92)g/ L,with statistically significant differences (t = 35. 874,P < 0. 001;t = 26. 633,P < 0. 001). The sensitivity of serum Cys-C for predicting short-term efficacy was 83. 0%,the specificity was 76. 6%,and those of serum β2-MG were 89. 3% and 73. 6% . The area under curve (AUC)of the serum Cys-C was 0. 813 (95% CI:0. 764-0. 862),and the AUC of serumβ2-MG was 0. 865 (95% CI:0. 825-0. 906),with a statistically significant difference (Z = 2. 490,P =0. 011). Spearman correlation analysis showed a positive correlation between serum Cys-C and β2-MG (r =0. 539,P = 0. 041). Logistic regression analysis showed that both β2-MG (95% CI:2. 386-5. 144,P <0. 001)and Cys-C (95% CI:2. 367-9. 702,P < 0. 001)were independent factors affecting the short-term effi-cacy of MM. Multivariate analysis showed that β2-MG (95% CI:3. 549-13. 739,P = 0. 001 )was an independent factor affecting the efficacy of MM. Conclusion The levels of serum Cys-C and β2-M in MM patients are significantly higher than those in healthy people,and they show an increasing trend with the pro-gression of MM disease,which can be used as markers for the pathological staging diagnosis of MM patients. The short-term efficacy of the patients can be evaluated by using the two indicators,and the clinical significance in efficacy evaluation of β2-MG is slightly better than that of Cys-C.
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Objective@#To explore the application value of serum cystatin C (Cys-C) and β2-microglobulin (β2-MG) in the diagnosis and short-term efficacy evaluation of multiple myeloma (MM).@*Methods@#A total of 450 patients with MM admitted to Anqing Hospital of Chinese People′s Liberation Army Navy and Jinhua Central Hospital of Zhejiang Province from October 2016 to October 2018 were selected as subjects (MM group), according to the Durie-Salmon staging criteria, including 150 patients in stage Ⅰ, Ⅱ and Ⅲ. A total of 150 healthy subjects were selected as the control group. The levels of Cys-C and β2-MG in the serum of the subjects were determined. The differences of Cys-C and β2-MG levels between the two groups and the MM patients with different Durie-Salmon stages were compared. The differences of Cys-C and β2-MG levels between the patients with different short-term efficacy were compared. The receiver operating characteristic (ROC) curve was used to analyze the value of the two indicators in the evaluation of MM efficacy, and the correlation between Cys-C and β2-GM was analyzed. Logistic regression analysis was used to analyze the multiple factors affecting the clinical efficacy of MM patients.@*Results@#The levels of Cys-C and β2-MG in the serum of the patients with MM were (2.11±0.78) mg/L and (6.07±3.08) g/L respectively, and those in the control group were (0.75±0.20) mg/L and (1.78±0.59) g/L, with significant differences (t=33.848, P<0.001; t=28.084, P<0.001). The Cys-C levels of Durie-Salmon stage Ⅰ, Ⅱ and Ⅲ patients were (0.99±0.21) mg/L, (1.36±0.17) mg/L and (3.07±1.02) mg/L respectively, and the difference was statistically significant (F=44.157, P<0.001). The β2-MG levels in the serum of patients with stage Ⅰ, Ⅱ and Ⅲ were (2.57±0.75) g/L, (4.66±1.43) g/L, (8.63±2.26) g/L respectively, and the difference was statistically significant (F=57.285, P<0.001). In all the patients, 338 patients were effective, accoun-ting for 75.11%, and 112 patients were ineffective, accounting for 24.89%. The levels of Cys-C and β2-MG in the serum of the effective MM patients were (1.28±0.23) mg/L and (2.82±0.78) g/L, and those of ineffective patients were (2.97±0.77) mg/L and (6.22±1.92) g/L, with statistically significant differences (t=35.874, P<0.001; t=26.633, P<0.001). The sensitivity of serum Cys-C for predicting short-term efficacy was 83.0%, the specificity was 76.6%, and those of serum β2-MG were 89.3% and 73.6%. The area under curve (AUC) of the serum Cys-C was 0.813 (95%CI: 0.764-0.862), and the AUC of serum β2-MG was 0.865 (95%CI: 0.825-0.906), with a statistically significant difference (Z=2.490, P=0.011). Spearman correlation analysis showed a positive correlation between serum Cys-C and β2-MG (r=0.539, P=0.041). Logistic regression analysis showed that both β2-MG (95%CI: 2.386-5.144, P<0.001) and Cys-C (95%CI: 2.367-9.702, P<0.001) were independent factors affecting the short-term efficacy of MM. Multivariate analysis showed that β2-MG (95%CI: 3.549-13.739, P=0.001) was an independent factor affecting the efficacy of MM.@*Conclusion@#The levels of serum Cys-C and β2-M in MM patients are significantly higher than those in healthy people, and they show an increasing trend with the progression of MM disease, which can be used as markers for the pathological staging diagnosis of MM patients. The short-term efficacy of the patients can be evaluated by using the two indicators, and the clinical significance in efficacy evaluation of β2-MG is slightly better than that of Cys-C.
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Objective@#To understand the needs of primary and secondary school students, parents and teachers for comprehensive sexuality education content, and to explore the applicability of comprehensive sexuality education content in China.@*Methods@#By using the method of stratified cluster sampling, 5 571 primary and middle school students and 4 835 parents from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) were selected for questionnaire survey. Depending on the physical health monitoring points of various provinces and cities, 176 sexuality education related teachers in nine regions were surveyed. The development of the questionnaire was based on the content framework of comprehensive sexuality education proposed in the International Technical Guidelines for Sexuality Education.@*Results@#Students had a higher demand for knowledge on the concepts of "relationship" (53.4% for primary school students, 57.6% for junior high school students) and "health and well-being skills" (71.1% for primary school students, 55.9% for junior high school students). Parents had higher demand for most comprehensive sexuality education content with the exception of lower need for "sex and sexual behavior (74.7% of primary school parents, 80.8% of junior high school parents)" and "sexual and reproductive health (primary parents 74.3%, junior high school parents 75.8%)". Teachers had a high demand for most comprehensive sexuality education content, but primary school teachers had a lower need for "values, rights, culture and sex(65.9%)", "sex and sexuality(60.1%)" and "sexual and reproductive health(66.8%)". The results of correspondence analysis showed that junior middle school teachers had the highest demand for comprehensive education content, followed by primary school parents, junior middle school parents, primary school teachers, junior middle school students and primary school students.@*Conclusion@#Teachers and parents have a higher demand for most comprehensive sexuality education content, while lower demand for some relatively sensitive content. Students have a relatively low demand for comprehensive sexuality education content. It is recommended to further improve the content of school sexuality education based on the actual needs of China.