Objective To explore the diagnostic value of electrocardiogram parameters combined with serum microRNA(miR)-322 and miR-568 levels in patients with chronic heart failure(CHF)complicated with ventricular arrhythmias(VA).Methods A total of 230 CHF patients admitted to Zhangjiakou First Hospital from April 2020 to April 2023 were selected as the study objects,including 120 VA patients(VA group)and 110 non VA patients(non VA group),and 110 patients who underwent health examinations in Zhangjiakou First Hospital during the same period as the control group.Compared three sets of general information,electrocardiogram parameters,left ventricular ejection fraction(LVEF),cardiac function grade and serum miR-322 and miR-568 levels.Logistic regression analyzed the influencing factors of VA in CHF patients.Receiver operating characteristic curve(ROC)analyzed electrocardiogram parameters combined with serum miR-322 and miR-568 for the diagnostic value of VA in CHF patients.Results The three groups showed statistically obvious differences in classification of nyha heart function(NYHA)and left ventricular ejection fraction(LVEF)(F=6.033,691.853,all P<0.05).The electrocardiogram parameters of CHF patients,including QT interval dispersion(QTD),QRS wave duration and corrected QT systolic time(QTc)were obviously higher than those in the control group(t=16.539,17.709,14.414),and the VA group were obviously higher than the non VA group(q=10.984,7.794,10.174),and the differences were statistically significan(all P<0.05).The serum levels of miR-322 and miR-568 were obviously lower than those in the control group(t=23.719,17.359).and the VA group were obviously lower than the non VA group(q=10.345,9.941),the differences were statistically significant(all P<0.05).Logistic regression analysis showed that NYHA grading,LVEF,QTD,QRS,wave duration,QTc,serum miR-322 and miR-568 levels were all influencing factors in the complication of VA in patients with CHF(Wald χ2=4.267～9.839,all P<0.05).The combination of electrocardiogram parameters and serum miR-322,miR-568 was better diagnosing CHF patients with concurrent VA that QTD,QRS duration,QTc and serum miR-332,miR-568 were measured separately.Conclusion Serum levels of miR-322 and miR-568 are obviously reduced,and the combination of electrocardiogram parameters with serum miR-322 and miR-568 has high diagnostic value for CHF patients with VA.

Objective:To investigate the relationship between the serum levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), S100 calcium binding protein B (S100B) with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes.Methods:The clinical data of 153 pregnant women with gestational diabetes (research group) and 153 healthy pregnant women (control group) in the Second Affiliated Hospital of Xi ′an Medical University from January 2020 to October 2023 were retrospectively analyzed. The serum levels of VEGF, MMP-9 and S100B were measured by enzyme linked immunosorbent assay, and the fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin and glycated hemoglobin were measured, and the homeostasis model assessment insulin resistance index (HOMA-IR) was calculated. The adverse outcomes of pregnant women with gestational diabetes were recorded. Pearson method was used to analyze the correlation between glycolipid metabolism indexes and VEGF, MMP-9, S100B in pregnant women with gestational diabetes. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcome in pregnant women with gestational diabetes. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of VEGF, MMP-9 and S100B on adverse pregnancy outcome in pregnant women with gestational diabetes. Results:The fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol, LDL-C, VEGF, MMP-9 and S100B in research group were significantly higher than those in control group: (9.42 ± 0.65) mmol/L vs. (4.13 ± 0.46) mmol/L, (16.58 ± 2.37) mU/L vs. (13.41 ± 2.05) mU/L, (7.28 ± 0.46)% vs. (4.35 ± 0.39)%, 4.83 ± 0.42 vs. 2.71 ± 0.37, (3.41 ± 0.67) mmol/L vs. (2.85 ± 0.63) mmol/L, (5.54 ± 1.56) mmol/L vs. (5.12 ± 1.50) mmol/L, (3.14 ± 0.97) mmol/L vs. (2.86 ± 0.93) mmol/L, (184.02 ± 30.25) ng/L vs. (156.33 ± 26.41) ng/L, (45.78 ± 7.56) μg/L vs. (29.36 ± 5.03) μg/L and (117.51 ± 25.12) ng/L vs. (89.74 ± 22.46) ng/L, the HDL-C was significantly lower than that in control group: (1.34 ± 0.27) mmol/L vs. (1.42 ± 0.30) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Pearson correlation analysis result showed that VEGF, MMP-9, S100B in pregnant women with gestational diabetes were positively correlated with fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol and LDL-C ( P<0.01), negatively correlated with HDL-C ( P<0.01). Among 153 pregnant women with gestational diabetes, 49 had adverse pregnancy outcome, and 104 had good pregnancy outcome. The VEGF, MMP-9 and S100B in pregnant women with adverse pregnancy outcome were significantly higher than those in pregnant women with good pregnancy outcome: (212.75 ± 28.63) ng/L vs. (170.49 ± 26.58) ng/L, (52.37 ± 7.14) μg/L vs. (42.68 ± 6.35) μg/L and (136.83 ± 23.62) ng/L vs. (108.41 ± 21.35) ng/L, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that VEGF, MMP-9 and S100B were independent risk factors for adverse pregnancy outcome in pregnant women with gestational diabetes ( OR = 7.013, 5.382 and 6.129; 95% CI 5.206 to 9.447, 3.449 to 8.398 and 3.520 to 10.673; P<0.01). ROC curve analysis result showed that the area under the curve of VEGF, MMP-9 combined S100B in predicting adverse pregnancy outcome in pregnant women with gestational diabetes was significantly larger than that of VEGF, MMP-9 and S100B alone (0.945 vs. 0.863, 0.847 and 0.801; P<0.05 or <0.01), with sensitivity of 89.80% and specificity of 91.30%. Conclusions:The high serum levels of VEGF, MMP-9 and S100B are associated with abnormal glycolipid metabolism and adverse pregnancy outcome in pregnant women with gestational diabetes, and the combination of the three indexes has a high predictive value for adverse pregnancy outcome.

[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.

Objective To explore the diagnostic value of electrocardiogram parameters combined with serum microRNA(miR)-322 and miR-568 levels in patients with chronic heart failure(CHF)complicated with ventricular arrhythmias(VA).Methods A total of 230 CHF patients admitted to Zhangjiakou First Hospital from April 2020 to April 2023 were selected as the study objects,including 120 VA patients(VA group)and 110 non VA patients(non VA group),and 110 patients who underwent health examinations in Zhangjiakou First Hospital during the same period as the control group.Compared three sets of general information,electrocardiogram parameters,left ventricular ejection fraction(LVEF),cardiac function grade and serum miR-322 and miR-568 levels.Logistic regression analyzed the influencing factors of VA in CHF patients.Receiver operating characteristic curve(ROC)analyzed electrocardiogram parameters combined with serum miR-322 and miR-568 for the diagnostic value of VA in CHF patients.Results The three groups showed statistically obvious differences in classification of nyha heart function(NYHA)and left ventricular ejection fraction(LVEF)(F=6.033,691.853,all P<0.05).The electrocardiogram parameters of CHF patients,including QT interval dispersion(QTD),QRS wave duration and corrected QT systolic time(QTc)were obviously higher than those in the control group(t=16.539,17.709,14.414),and the VA group were obviously higher than the non VA group(q=10.984,7.794,10.174),and the differences were statistically significan(all P<0.05).The serum levels of miR-322 and miR-568 were obviously lower than those in the control group(t=23.719,17.359).and the VA group were obviously lower than the non VA group(q=10.345,9.941),the differences were statistically significant(all P<0.05).Logistic regression analysis showed that NYHA grading,LVEF,QTD,QRS,wave duration,QTc,serum miR-322 and miR-568 levels were all influencing factors in the complication of VA in patients with CHF(Wald χ2=4.267～9.839,all P<0.05).The combination of electrocardiogram parameters and serum miR-322,miR-568 was better diagnosing CHF patients with concurrent VA that QTD,QRS duration,QTc and serum miR-332,miR-568 were measured separately.Conclusion Serum levels of miR-322 and miR-568 are obviously reduced,and the combination of electrocardiogram parameters with serum miR-322 and miR-568 has high diagnostic value for CHF patients with VA.

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

Premature ovarian insufficiency(POI)is a disease that seriously affects the health and life of women,which is also one of the main causes of female infertility.The incidence of POI is increasing in recent years.The diagnostic criteria of POI are not uniform,and different diagnostic criteria have inconsistent thresholds for various indicators.Strict diagnostic criteria are more conducive to early detection and treatment of POI.At present,complementary and alternative therapies such as traditional Chinese medicine,acupuncture and moxibustion are widely used in the treatment of POI.This article reviewed the recent studies on the complementary and alternative therapy of traditional Chinese medicine in the treatment of POI,and finds that the dialectical treatment of traditional Chinese medicine is based on the perspective of traditional Chinese medicine theory and puts forward corresponding treatment plans for different dialectical types.For example,treatment from the kidney,tonifying kidney filling essence,regulating chongren;Treatment from the liver,soothing the liver,regulating qi,nourishing blood and softening the liver;Treatment from the heart and spleen,nourishing Yangming,tonifying the spleen and nourishing the heart.In terms of acupuncture treatment,regulating menstruation and promoting pregnancy and regulating the conception vessel and toning the governor vessel and toning the kidney are often used to treat POI.In addition,moxibustion regulates body function by stimulating the bladder meridian and conception vessel and governor vessel acupoints.Other methods,such as ear acupoint bean-pressing,acupoint thread-embedding and acupoint injection,have also shown potential in the treatment of POI.This article summarizes the role and characteristics of traditional Chinese medicine in the treatment of POI,in order to provide ideas and basis for clinical treatment of POI.

OBJECTIVE: To explore the molecular mechanism of a case with RhD-- phenotype. METHODS: A proband with RhD-- phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband's variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-- phenotype protein were constructed to predict the alterations of the RhD-- phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). RESULTS: The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD--. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE*cE (c.365C>A)/RHCE*cE (c.365C>A) and RHCE*Ce/RHCE*cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-- type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. CONCLUSION Above results revealed the molecular biological mechanism of a RhD-- phenotype. The c.365C>A variant in the RHCE gene has rendered the RHCE*cE alleles invalid, which ultimately led to the RhD-- phenotype.
Humans ; Rh-Hr Blood-Group System/chemistry* ; Female ; Phenotype ; Male ; Alleles ; Pedigree ; Base Sequence ; Molecular Sequence Data ; Adult

Objective To explore the role and mechanism of HJT-sRNA-m7(M7)bencaosome in a silicosis mouse model.Methods C57BL/6J mice were randomly divided into four groups:blank,control,negative control(NC)oligonucleotide,and M7 treatment(HJT-sRNA-m7 bencaosome)groups.After three rounds of pretreatment with HJT-sRNA-m7 bencaosome,all groups except the blank one were modeled via a single intratracheal exposure.Each mouse received 50 μL of a silica suspension at a dose of 200 mg/kg body weight via intratracheal instillation.From day 6 to day 26,the bencaosome was administered every other day via oral gavages.On day 28,pulmonary function tests were performed.Bronchoalveolar lavage fluid was collected for flow cytometry and cytokine analysis.The left lung was harvested for histopathological examination and Masson's trichrome staining to evaluate collagen fiber dep-osition.The right lung was used for hydroxyproline quantification to assess collagen accumulation.Results The re-sults of pulmonary function test,pathological analysis and hydroxyproline measurements all indicated that M7 ben-caosome treatment significantly alleviated silica-induced pulmonary fibrosis.Moreover,flow cytometry analysis of BALF confirmed that M7 bencaosome inhibited the silica-induced inflammatory response,that was supported by cy-tokine analysis.Conclusions HJT-sRNA-m7 bencaosome is quite effective to treat silicosis and inhibits mitigating pulmonary fibrosis progression in mouse models.

Objective:To explore the molecular mechanism of a case with RhD-phenotype.Methods:A proband with RhD-phenotype who attended the clinic of the First Affiliated Hospital of Zhengzhou University on January 29, 2024 was selected as the study subject. Peripheral blood samples were collected from the proband (8 mL) and her close relatives (father, mother and brother; 3 mL each) for Rh phenotyping and irregular antibodies testing with gel card and test tube methods. Direct agglutination reaction and absorption-elution test were used to detect the c antigen on the red blood cells of the proband. PCR-sequence specific primers (PCR-SSP) typing and gene sequencing were used to determine the RHCE gene of the proband and her relatives. The origin of the proband′s variant was traced by pedigree analysis. Three-dimensional structural models of the wild-type RhCE*cE protein and the RhD-phenotype protein were constructed to predict the alterations of the RhD-phenotype protein caused by the variant. The procedures of this study were approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No.: 2023-KY-0870-003). Results:The red blood cells of the proband did not agglutinate with anti-C, anti-c, anti-E, and anti-e. The result of the serum irregular antibody test was negative. The results of direct agglutination reaction and absorption-elution test of the proband were both negative. Her Rh blood group was identified as RhD-. The results of the Rh blood grouping of her close relatives were normal. PCR-SSP detection showed that the RHCE genotypes of the proband and her close relatives were cE/cE and Ce/cE, respectively. Gene sequencing analysis showed that the RHCE genotypes of the proband and her close relatives were RHCE* cE (c.365C>A)/ RHCE* cE (c.365C>A) and RHCE* Ce/ RHCE* cE (c.365C>A), respectively. Pedigree analysis revealed that the variants in the proband were inherited from her father and mother, respectively. Homology modeling of RhCE*cE protein showed that the RhD-type peptide chain with a significantly shortened C-terminal was encoded by only 121 amino acid resides, which was 296 amino acid resides shorter compared to the wild-type RhCE*cE peptide chain encoded by 417 amino acid residues. Conclusion:Above results revealed the molecular biological mechanism of a RhD-phenotype. The c. 365C>A variant in the RHCE gene has rendered the RHCE* cE alleles invalid, which ultimately led to the RhD-phenotype.