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

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

OBJECTIVE: To explore a predictive model that can better predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), and validate its clinical value. METHODS: Clinical data of 134 newly treated DLBCL patients were collected from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020. Several risk factors of the patients were screened and analyzed, a novel prognostic model were then established based on this, and its clinical application potential was validated. RESULTS: In the novel model, predicting progression-free survival (PFS) based on the age at initial treatment, albumin level, Hans classification, Ann Arbor stage, and BCL2 expression showed better predictive performance than International Prognostic Index (IPI) score (AUC: 0.788 vs 0.620，P <0.001). Predicting overall survival (OS) based on the age at initial treatment, albumin level, lactate dehydrogenase (LDH) level, and expressions of BCL2 and MUM1 proteins also showed better predictive performance for mortality risk than IPI score (AUC: 0.817 vs 0.624，P <0.001). CONCLUSION This novel prognostic model can better predict the survival prognosis of DLBCL patients compared to the IPI scoring system.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Risk Factors ; Male ; Female ; Middle Aged

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.

Objective:To investigate the clinical features and family gene mutation results of the adult onset Gaucher disease patient.Methods:The diagnosis and treatment of a patient with Gaucher disease who was admitted to the Affiliated Zhongshan Hospital of Dalian University in March 2020 were retrospectively analyzed, and the literature was reviewed.Results:The patient (the proband) was a 34-year-old female, the anemia, thrombocytopenia and splenomegalia were found in 2005. After regular physical examination, the decrease of leukocyte, red blood cell and platelet was gradually aggravated, and the progressive enlargement of the spleen was aggravated. She visited the clinic on March 19, 2020 due to worsening of fatigue. The physical examination revealed hepatomegaly, splenomegaly; blood routine examination showed pancytopenia, and bone marrow morphology showed a large number of Gaucher cells. Peripheral blood β- glucocerebrosidase (GBA) of the proband was 1.8 nmol·mg -1·h -1 (reference value 10-25 nmol·mg -1·h -1), and the GBA of her father, mother, brother, and daughter was normal. The second-generation sequencing results showed that the proband had a mutation in the BCL2 gene at locus c.127G>A p.A43T, with a mutation frequency of 49.53%. GBA gene testing showed that the proband had a heterozygous mutation at c.1448T>C (a pathogenic mutation), heterozygous mutations at c.1026A>G and c.1038C>T (homozygous mutations), and a heterozygous mutation at c.1075G>T (mutation of unknown clinical significance). The proband's father had c.1448T>C heterozygous mutation, and he was a carrier; the proband's mother had c.1075G>T heterozygous mutation; the proband's brother had no gene mutation; the proband's daughter had c.1448T>C heterozygous mutation, and she was a carrier. The diagnosis was type Ⅰ Gaucher disease (non-neuropathic). The patient was proposed to participate in the clinical trial of imiglucerase, and during the follow-up, the blood routine was relatively stable, and the spleen remained progressively enlarged. Conclusions:Gaucher disease is rare, which is easy to be misdiagnosed and underdiagnosed. It is necessary to be alert to the possibility of Gaucher disease when there are patients with unexplained hemocytopenia, liver and spleen enlargement and multiple organs involvement, and enzyme and genetic tests should be performed as soon as possible.

Objective:To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms(SNP)on semen quality in men.Methods:We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023,33 from oligozoospermia(OS),97 from asthenozoospermia(AS)and 54 from oligoas-thenozoospermia(OAS)patients and the other 100 from normal men.We performed computer-assisted semen analysis(CASA)of the samples,extracted blood DNA and,using the Mass ARRAY? System,genotyped the target genes,determined the genotypes of 13 SNPs and compared their distribution,their correlation with BMI and semen quality in different groups.Results:The mutant homozygous(TT)genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS(OR=4.420,P=0.047),while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous(TC)genotype important protective factors for OS(OR=0.422 and 0.389;P=0.045 and 0.043,respectively).A significantly higher sperm concentration was found associated with the MC4R rs17782313 heter-ozygous(TC)genotype than with the homozygous(CC)genotype.Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes.Conclusion:FADS2 rs2727270,APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

Objective To understand the current situation of protective mask wearing behavior of health care workers(HCWs),analyze the influencing factors for the failure to wear medical protective masks in a standard manner,and provide basis for the improvement of mask-wearing related training.Methods From June 2022 to March 2023,staff in a tertiary first-class hospital were selected as the research object.Real-time quantitative fitness testing using aerosol condensation particle counting method was applied to test 5 commonly used medical protective masks available in the market.Fitness factor changes of the testing instrument and assistance from professional per-sonnel were needed to comprehensively estimate the wearing condition of medical protective masks.Participants were surveyed through a self-made general information questionnaire.Heads and faces of participants were scanned by three-dimensional(3D)laser scanning technology,and scanned images were imported into Geomagic Studio 2013 software to measure head and face dimensions.Results A total of 222 HCWs were investigated,991 real-time tests and 208 times of 3D scanning were conducted.221(22.30％)tests showed failure of participants in wearing masks in a standard manner.The non-standard wearing rates of 5 types of medical protective masks were 30.56％,25.62％,25.87％,23.15％,and 7.35％,respectively.The non-standard mask-wearing rates showed statistically significant difference between groups categorized in terms of medical protective masks with different shapes,partici-pants'occupation,time of last training for wearing medical protective masks,and participants'experience in pre-vention and control of respiratory infectious disease(all P＜0.05).There were no statistically significant differences in non-standard mask-wearing rate between groups with different brands and sizes of medical protective masks,as well as gender and department of participants,etc.(all P＞0.05).The body mass index(BMI)was significantly different among participants who wear foldable medical protective masks in the standard and non-standard manner(both P＜0.05).Conclusion Wearing medical protective masks by HCWs in a non-standard manner is influenced by multiple factors.It is recommended to conduct real-time testing before formal quantitative fitness testing,so as to save time and improve testing efficiency.When conducting training on wearing medical protective masks in the fu-ture,targeted training should be provided based on mask shape and focus on logistics personnel,interns,individuals with high BMI,those who have never received training on wearing medical protective masks,and those who have never participated in the prevention and treatment of respiratory infectious diseases.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.