A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Objective To investigate the association of digit ratio with single nucleotide polymorphism(SNP)at three loci(rs17576,rs3918249,rs9509)of matrix metallopeptidase 9(MMP-9)gene.Methods A total of 804 Ningxia Han youths(399 males and 405 females)were used as the study subjects.A digital camera was used to take frontal photographs of the hands,and image analysis software was used to mark the anatomical points and measure the lengths of each finger of both hands(2D,3D,4D,5D);Multiplexed PCR was used to detect the three polymorphic sites of the MMP-9 gene,SPSS 25.0 and R Studio software were used for data analysis and plotting.Results The 2D/3D(P＜0.05)and 2D/4D(left,P＜0.01,right,P＜0.05)of both hands,2D/5D(P＜0.01),3D/5D,4D/5D(P＜0.05)of the right hand,and 3D/4D(P＜0.05)of the left hand in female youths of Ningxia Han were significantly higher than those in males,Differences in genotypes and allele frequencies at all 3 loci of the MMP-9 gene were not statistically significant between genders(P＞0.05).Right hand 2D/4D was significantly associated with genotypes at the rs17576 and rs3918249 loci in male youths(P＜0.05).Conclusion MMP-9 gene SNPs(rs17576 and rs3918249)may be associated with the formation of 2D/4D of Ningxia Han male youths.

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To compare ocular surface dry eye-related indexes and tear cytokine level changes in chronic ocular graft-versus-host disease (oGVHD) patients after receiving topical treatment of 0.05% cyclosporine or 0.1% tacrolimus eye drops.Methods:A randomized controlled study was conducted.A total of 60 chronic oGVHD patients (60 eyes) were recruited at Beijing University Third Hospital from April 2020 to April 2021.The patients were divided into tacrolimus group and cyclosporine group by a random number table, with 30 patients (30 eyes) in each group.Patients in tacrolimus group used 0.1% tacrolimus eye drops (twice a day) and patients in cyclosporine group used 0.05% cyclosporine eye drops (4 times a day).Additionally, 0.1% flumetholon (twice a day), deproteinized calf blood extract (3 times a day), and 0.1% sodium hyaluronate eye drops (8 times a day) were applied for anti-inflammation and lubrication in both groups.Patients were screened according to exclusion criteria after 1-month treatment.Eventually, 21 patients (21 eyes) in tacrolimus group and 12 patients (12 eyes) in cyclosporine group were included for further study.Patients were examined before and 1 month after treatment.The primary evaluation indexes included Ocular Surface Disease Index (OSDI), corneal fluorescein staining scores and tear film break-up time (BUT).Expressions of interleukin (IL)-6, IL-8, IL-17, epidermal growth factor (EGF), and tumor necrosis factor-α (TNF-α) in tears were detected before and after treatment using Luminex chip.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.M2020489).Written informed consent was obtained from each subject before any medical examination.Results:The OSDI differences between before and after treatment were 0.4(-5.6, 2.5) in tacrolimus group and 27.2(4.6, 45.0) in cyclosporine group, and the OSDI improvement was significantly greater in cyclosporine group than in tacrolimus group ( Z=-2.547, P=0.009).The differences of corneal fluorescein staining scores and BUT between before and after treatment were 5.0(2.5, 10.0) scores and 3.5(-0.5, 13.8) seconds in tacrolimus group, 0.0(-3.0, 0.0) scores and -1.5(-3.0, 0.0) seconds in cyclosporine group, respectively, with no significantly difference between both groups ( Z=-0.526, -0.804; both at P>0.05).The differences of IL-6, IL-8, IL-17, EGF and TNF-α expressions between before and after treatment in tacrolimus group and cyclosporine group were not significantly different ( Z=-0.487, -0.112, -0.412, -1.085, -1.198; all at P>0.05). Conclusions:Altered levels of all tested cytokines in oGVHD tears are of no significant differences between tacrolimus and cyclos porine treatment.In addition, 0.05% cyclosporine eye drops may be more comfortable than 1% tacrolimus for chronic oGVHD patients.

Objective To investigate the relationship between digit ratio and schizophrenia in men from Ningxia Han nationality. Methods Using anthropometry, digital camera was used to obtain finger photographs of both hands of 216 male subjects (nonnal control; 116, schizophrenia patient; 100). The anatomical points were marked and the length of each finger of both hands were measured by computer image analysis software (Image-Pro Plus 6 . 0 ) . Differences of the mean digit ratio of left and right hand 2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D between the control group and the patient group were compared. The correlation between 2D :4D and onset age in the patient group were analyzed. Results Except for left and right hand 3D :4D, digit ratios in patient group were significantly higher than those in control group (2D :4D and 3D :5D in both hands, right hand 3D :5D, p all<0. 001; 2D :3D and 4D :5D, left hand 3D :5D, P<0. 0 1 ) . Compared with the control group (left hand; 1%, right hand; 1%) , the percentage of 2D:4D Ss 1 were significantly higher ( P<0. 05) in the patient group (left hand; 6% , right hand; 7%). There were no conelations between 2D :4D mean value and onset age in patients group (P>0. 05). Conclusion Digit ratio is related to the occurrence of schizophrenia in Ningxia Han male.

Objective To investigate the association between 8 single-nucleotide polymorphisms (SNPs) of hydroxysteroid dehydrogenase (HSD) gene family and human digit ratio (2D ∶ 4D). Methods Randomly selected 808 college students (400 males and 408 females) as subjects, the digit ratio of left and right fingers were measured and calculated using computer image software. Eight SNPs (rs1000283, rs2236903, rs5479, rs56303414, rs676387, rs4445895, rs2066474, rs8190478) in HSD11B and HSD17B gene families were genotyped by multiplex PCR. The association between 2D ∶4D and different genotypes was analyzed by One-Way ANOVA. Results Female left hand(L)2D ∶ 3D, L2D ∶4D, L3D ∶4D, right hand(R)2D ∶4D, R2D ∶5D were significantly higher than male (P<0. 05). The genotype frequency of rs2236903 (HSD11B1) was significantly different between male and female (P < 0. 05). A good linkage disequilibrium was found between rs1000283and rs2236903 of HSD11B1 gene, rs5479 and rs56303414 of HSD11B2 gene, but there was no statistical difference in frequency between male and female students(P>0. 05). The genotypes frequency of the 8 SNPs were not significantly associated with digit ratio (2D ∶4D) in both males and females (P>0. 05). Conclusion There are significant gender differences in digit ratio in Ningxia Han college students, but there is no correlation between digit ratio and 8 SNPs in HSD11B and HSD17B gene families, suggesting that HSD11B and HSD17B gene families may have nothing to do with the formation of human digit ratio.

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 10⁷ CFU/ml and 10⁸ CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 10⁴ CFU/ml. Detection sensitivity of Yersinia pestis ≥10³ CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥10³ CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 10⁴ CFU/m³, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.
Humans ; Sensitivity and Specificity ; Technology