Cardiac myosin binding protein-C(cMyBP-C),as an important component of myocardium coarse filaments,can regulate cross-bridge circulation through phosphorylation or dephosphorylation and participates in myocardial systolic and diastolic functions.cMyBP-C plays an important role in the occurrence and development of cardiovascular diseases(CVDs)such as acute myocardial infarction,cardiomyopathy,heart failure,aortic stenosis,hypertensive myocardial hypertrophy,and myocarditis,but the specific mechanism has not been fully clarified.This article reviews the research progress on the role of cMyBP-C in CVDs,in order to provide references for the diagnosis,treatment and prognosis evaluation of CVDs.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

OBJECTIVE: To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection. METHODS: We investigated the increases in IP10 signals, primarily localized in neurons within the brains of scrapie-infected mice, using western blotting, ELISA, co-immunoprecipitation, immunohistochemistry, immunofluorescence assays, and RT-PCR. RESULTS: Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia. Morphological colocalization of PrP ^C/PrP ^Sc with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence. immunohistochemistry (IHC) analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrP ^Sc deposits. Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3. Notably, a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line, SMB-PS. Importantly, resveratrol treatment effectively suppressed prion replication in SMB-S15 cells, thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells. CONCLUSION Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrP ^Sc deposition. Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.
Animals ; Receptors, CXCR3/metabolism* ; Mice ; Chemokine CXCL10/metabolism* ; Brain/metabolism* ; Scrapie/metabolism* ; Signal Transduction ; PrPSc Proteins/metabolism*

Objective Prior studies have established a connection between albuminuria and various inflammatory reactions,highlighting that an increase in C-reactive protein by 1 mg/L increases the likelihood of albuminuria by 2%.Recent investigations indicate a positive correlation between the systemic immune-inflammation index(SII)and increased urinary protein excretion.In addition,elevated levels of the systemic inflammatory response index(SIRI)also correlate with a higher prevalence of albuminuria.The aggregate index of systemic inflammation(AISI)offers a more comprehensive indicator of inflammation,providing an extensive assessment of systemic inflammatory status compared to SII and SIRI.Yet,the specific relationship between AISI and albuminuria remains unclear.This study aims to explore this association in U.S.adults.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)for 2007-2018,excluding pregnant women and individuals under 18.Cases with missing data on AISI,urinary albumin concentration,and other covariates were also excluded.AISI was computed using the formula:AISI=(platelet count×neutrophil count×monocyte count)/lymphocyte count.Albuminuria was defined as the urinary albumin-to-creatinine ratio exceeding 30 mg/g.Continuous variables were presented in the form of the mean±standard error,and categorical variables in percentages.We utilized weighted t-tests and chi-square tests for baseline comparisons.We applied weighted multivariable logistic regression and generalized additive models(GAM)to explore the association between AISI and albuminuria and to assess potential nonlinear relationships.Results The study included 32 273 participants,with an average age of(46.75±0.24)years old.The cohort comprised 48.73% males and 51.27% females.The prevalence of albuminuria was 9.64%.The average logarithmic value of log2AISI was 7.95±0.01,and were categorized into tertiles as follows:Quartile 1(Q1)(4.94 to 7.49),Q2(7.49 to 8.29),and Q3(8.29 to 10.85).As log2AISI increased,so did the prevalence of hypertension,diabetes,congestive heart failure,and albuminuria,all showing statistically significant increases(P<0.001).Similarly,the use of antihypertensive,lipid-lowering,and hypoglycemic drugs was also more prevalent(P<0.001).Statistically significant differences were observed across the three groups concerning age,race and ethnicity,formal education,alcohol consumption,smoking status,systolic and diastolic blood pressures,body mass index,estimated glomerular filtration rate,HbA1c,alanine aminotransferase,aspartate aminotransferase,albumin,creatinine,uric acid,and high-density lipoprotein cholesterol(P<0.05).However,no significant differences were noted in the total cholesterol or the sex ratios among the groups.The association between log2AISI and albuminuria was assessed using weighted multivariable logistic regression,and the detailed results are presented in Table 2.In model 1,without adjusting for covariates,each unit increase in log2AISI was associated with a 32% increase in the risk of albuminuria(odds ratio[OR]=1.32,95% confidence interval[CI]:1.27-1.38,P<0.001).Model 2 was adjusted for age,gender,race,and education level,and showed a similar trend,with each unit increase in log2AISI associated with a 31% increased risk(OR=1.31,95% CI:1.26-1.37,P<0.001).Model 3,which was further adjusted for all covariates,revealed that each unit increase in log2AISI was associated with a 20% increase in the risk of albuminuria(OR=1.20,95% CI:1.15-1.26,P<0.001).The study also transformed log2AISI from a continuous to a categorical variable for analysis.Compared with Q1,the risk of albuminuria in Q3,after adjusting for all covariates,significantly increased(OR=1.37,95% CI:1.22-1.55,P<0.001).Q2 also demonstrated a higher risk compared with Q1(OR=1.13,95% CI:1.06-1.36,P=0.004).The trend test indicated a dose-effect relationship between increasing log2AISI and the rising risk of albuminuria.GAM revealed a nonlinear relationship between log2AISI and albuminuria,with distinct trends noted between sexes.Segmented regression based on turning points showed significant effects among women,although the slope difference between the segments was not significant.In men,a significant threshold effect was observed;below the log2AISI of 7.25,increases in log2AISI did not enhance the risk of albuminuria,but above this threshold,the risk significantly increased.As part of a sensitivity analysis,weighted multivariable logistic regression was performed by changing the outcome variable to macroalbuminuria and adjusting for all covariates.The analysis showed that for every unit increase in log2AISI,the risk of developing macroalbuminuria increased by 31% (OR=1.31,95% CI:1.15-1.49,P<0.001).Compared with Q1,the risk of albuminuria in Q3 increased by 69% (OR=1.69,95% CI:1.27-2.25,P<0.001),and in Q2,it increased by 40% (OR=1.40,95% CI:1.03-1.92,P=0.030).Subgroup analysis and interaction results showed that the positive association between AISI and proteinuria risk was stronger in men than in women.Similarly,the association was stronger in people with hypertension compared with those with normal blood pressure,and higher in overweight people compared with those of normal weight.Furthermore,smokers and drinkers showed a stronger positive association between AISI and the risk of proteinuria than non-smokers and non-drinkers do.These results suggest that sex,blood pressure,body mass index,smoking,and alcohol consumption interact with AISI to influence the risk of proteinuria.Conclusion There is a robust positive association between AISI and increased risks of albuminuria in US adults.As log2AISI increases,so does the risk of albuminuria.However,further validation of this conclusion through large-scale prospective studies is warranted.

Abstract OBJECTIVE To identify and analyze two unknown degradation impurities in nimodipine oral solution. METHODS The chemical structure of the unknown impurity was deduced by two-dimensional liquid chromatography-high resolution mass spectrometry(2DLC-HRMS), and the impurity monomer was obtained by directional synthesis. The structure of the impurity was confirmed by 1H-NMR and 13C-NMR, chromatographic separations were performed on an Thermo Syncronis C18(250 mm×4.6 mm, 5 μm) column. Using 5 mmol·L-1 potassium dihydrogen phosphate buffer(pH 2.8) as mobile phase A, while methanol-acetonitrile(50:50) was mobile phase B, with gradient elution. The mobile phase was pumped at 1.0 mL·min-1. The column temperature was 30℃. The detection wavelength was 235 nm. RESULTS Nimodipine and its related substances had good separation. The correction factors of every impurities ranged from 0.8 to 1.1. CONCLUSION The established method has good specificity and can effectively isolate and determine the related substances in nimodipine oral solution. This study provides a reference to guide the impurity control of nimodipine oral solution and other dosage forms.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Objective:To investigate the clinical value of referral colposcopy in cervical high-risk human papillomavirus (HR-HPV) positive women in cervical cancer screening.Methods:Totally 2 445 cases, which were referred for colposcopic cervical biopsy for cervical HR-HPV positive in Karamay Central Hospital from January 2018 to November 2021 were collected. The status of cervical HR-HPV positive transferred colposcopy in different situations to identify high-grade squamous intraepithelial lesions (HSIL) and above (HISL+ ) was analyzed. The value of referral colposcopy in cervical HR-HPV positive women under different conditions was evaluated.Results:2 445 HR-HPV positive women were referred for colposcopic cervical biopsy, which confirmed 1 447 cases of negative for intraepithelial lesion or malignancy (NILM), 362 cases of low grade squamous intraepithelia lesion (LSIL), 510 cases of HSIL and 126 cases of squamous cell carcinoma (SCC); The complete coincidence rate between colposcopy diagnosis and pathological diagnosis was 67.08%(1 640/2 445), and the Kappa value of consistency test was 0.489. The sensitivity and specificity of colposcopy in the diagnosis of LSIL+ were 91.28% and 69.38%, and HSIL+ were 74.52% and 93.15%. The detection rates of HSIL+ in HPV16/18 positive and other 12 HPV positive patients with abnormal cervical liquid based cytology (TCT) were 64.78%(103/159) and 78.79%(364/462), respectively. The positive rates of HPV16/18 and 12 other HPV positive HSIL+ with normal TCT were 16.46%(82/498) and 6.56%(87/1 326), respectively. The rate of detecting HSIL+ in abnormal areas under colposcopy was 44.69%(534/1 195), and that in routine biopsy was 8.16%(102/1 250).Conclusions:Among the referred for colposcopic cases, the detection rate of HSIL+ was higher in cases with cervical HR-HPV positive and TCT abnormalities. Colposcopy has obvious value in identifying cervical lesions. The accurate diagnosis of cervical lesions is based on cervical biopsy under colposcopy.

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.