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

ObjectiveThis study aims to explore the effect of ultrasound-guided superficial parasternal intercostal plane block on the quality of recovery and postoperative analgesia in patients undergoing sternotomy cardiac surgery. MethodsA total of 64 patients undergoing sternotomy cardiac surgery were selected for this study. They were randomly divided into two groups： one group received a superficial parasternal intercostal plane block with ropivacaine （the ropivacaine group）， while the other was given normal saline （the normal saline group）. The primary outcome was the Quality of Recovery-15 （QoR-15） score on postoperative day 1 in both groups， accompanied by a comparative analysis of the pain score and opioid usage. ResultsCompared with the normal saline group， the ropivacaine group exhibited a significantly higher QoR-15 score on postoperative day 1［（89.60±13.24） vs （81.18±12.78）， P=0.012］. The numerical rating scale at rest was significantly lower［（3.03±0.72） vs （4.26±0.93）， P<0.001］， and the numerical rating scale during coughing was also significantly reduced ［（4.40±0.89） vs （5.44±1.05）， P<0.001］. Concurrently， the cumulative morphine equivalent consumption during the initial 24 h postoperatively was significantly lower in patients who were administered the ropivacaine ［14.15 （4.95～30.00） mg vs 40.50 （19.25～68.18） mg， P=0.002］， and there was also a notable decrease in the rescue analgesia ［0.00 （0.00～0.00） mg vs 0.00 （0.00～100.00） mg， P=0.007］. ConclusionUltrasound-guided superficial parasternal intercostal plane block can significantly enhance the overall quality of recovery in patients undergoing sternotomy cardiac surgery on postoperative day 1. The technique contributes to improved postoperative analgesic effects and a reduction in opioid usage， thereby facilitating early postoperative recovery.

ObjectiveTo investigate the value of reduced field-of-view DWI （r-FOV DWI） in quantitative assessment of axial spondyloarthritis. MethodsA total of 112 patients with chronic back pain or suspected axial spondyloarthritis receiving full field-of-view DWI （f-FOV DWI） and reduced field-of-view DWI （r-FOV DWI） from December 2019 to December 2021 were enrolled. Next， subjective image quality assessment （anatomical detail， artifacts， distortion， overall image quality） and objective image quality assessment including （signal to noise ratio and contrast to noise ratio） were conducted by two experienced radiologists. In addition， the Apparent Diffusion Coefficient （ADC） values of three groups （active group， inactive group， and control group） on the two DWI sequences were measured by the two radiologists， respectively. Finally， the consistency of measurement between the two researchers was evaluated and the differences in ADC values was compared. Results102 patients were included and were divided into three groups， including the active group （n=32）， inactive group （n=29）， and control group （n=41） according to ASAS diagnostic criteria. All subjective and objective image quality metrics were rated in favor of r-FOV DWI images compared with f-FOV DWI images ［overall image quality： DWI 4（3~4） vs. 3（3~3） and SNR： 6.58（5.05~10.38） vs. 4.46（2.37~10.04）， CNR： 2.04（-1.14~8.29） vs. 0.97（-8.19~7.12）；P＜0.05］. Inter-rater consistency of the two researchers were 0.60~0.74. According to the AUC curve， group inactive vs. control showed r-FOV DWI was better than f-FOV DWI. In other groups （lesion vs. control， active vs. inactive）， there were no differences between both sequences（P＜0.05）. ConclusionThe subjective image quality score and signal to noise ratio of r-FOV DWI were higher than those of f-FOV DWI， which could be used for quantitative assessment of axial spondyloarthritis.

OBJECTIVE: To study and analyze the diagnostic value and interventional treatment value of high-frequency ultrasound for elbow cyst. METHODS: From February 2018 to February 2021, the data of 60 patients with elbow cyst treated by high-frequency ultrasound interventional therapy were retrospectively analyzed, including 30 males and 30 females with an average age of (30.93±5.32) years old ranging from 20 to 54 years old. The course of disease ranged from 1 to 10 years with an average of (3.45±0.25) years. High-frequency ultrasound features of all patients were analyzed. The clinical efficacy, the occurrence of adverse events and the changes of psychological status before and after treatment were analyzed. RESULTS: In 60 cases of elbow cyst, the cyst size was from 6 mm×7 mm to 111 mm×60 mm. The characteristics of ultrasonic images included such as most of the morphology was regular, which was round or oval, and a few were irregular;the boundary was clear, there was a capsule wall, most of the inside of the capsule was good, no echo;when accompanied by bleeding or infection, small dense points can be seen floating;the cystic wall of the patients with long course of disease was coarser, and the internal light bands were separated, showing multilocular shape;no significant blood flow signal was observed. Final results involved olecranon bursa cysts in 19 cases, annular ligament cysts in 10 cases, radial bursa cysts in 9 cases, accessory ligament cysts in 7 cases, epidermoid cysts in 4 cases, ganglion cysts in 6 cases, nerve sheath cysts in 5 cases. After treatment, 33 cases were cured, 16 cases had obvious effect, 11 cases were improved, 0 cases were invalid. After treatment, mild adverse events occurred in 1 case, moderate adverse events in 1 case, and severe adverse events in 0 cases, with a total incidence of 3.33% (2/60). After treatment, positive affect score (38.04±1.74) was higher than that before treatment (35.92±2.34), and negative affect score (24.61±1.51) was lower than that before treatment (30.15±3.46), with statistical significance(P<0.05). CONCLUSION High-frequency ultrasound has high diagnostic value for elbow cyst, and it has ideal effect in interventional therapy.
Male ; Female ; Humans ; Adult ; Young Adult ; Middle Aged ; Retrospective Studies ; Elbow ; Cysts ; Ultrasonography ; Treatment Outcome

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ²=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.
Male ; Humans ; Female ; Adult ; Middle Aged ; Cross-Sectional Studies ; Early Detection of Cancer/methods* ; Colorectal Neoplasms/pathology* ; Colonoscopy/methods* ; Mass Screening/methods* ; Adenoma/diagnosis* ; DNA ; Syndecan-2/genetics*

Animals ; Cell Proliferation ; Hepatic Stellate Cells ; Liver Cirrhosis/metabolism* ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Rats

Child ; Cord Blood Stem Cell Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Primary Myelofibrosis/therapy* ; Thiotepa ; Transplantation Conditioning

OBJECTIVE: To observe the efficacy of acupuncture on symptom burden in patients with gastric cancer during adjuvant chemotherapy after gastrectomy. METHODS: A total of 58 patients were randomized into a high-dose acupuncture group (19 cases, 5 cases dropped off), a low-dose acupuncture group (20 cases, 6 cases dropped off) and a control group (19 cases, 2 cases dropped off). Conventional chemotherapy and antiemetic treatment were adopted in the control group. On the basis of the treatment in the control group, acupuncture was applied 7 times each chemotherapy cycle for totally 21 times in the high-dose acupuncture group, and 3 times each chemotherapy cycle for totally 9 times in the low-dose acupuncture group. Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc. were selected in the two acupuncture groups, as well as back-shu points selected by the meridian heat sensing technique. Electroacupuncture was connected to ipsilateral Zusanli (ST 36) and Neiguan (PC 6), with continuous wave, 2 Hz in frequency for 20 min. The Edmonton symptom assessment system (ESAS) score was observed on day 1-7, 14, and 21 of each cycle of chemotherapy respectively in the 3 groups. RESULTS: The symptom burden was worst within 7 days of each cycle of chemotherapy in the 3 groups. After the 3rd chemotherapy cycle, the total score of ESAS in the low-dose acupuncture group was lower than the control group (P<0.05), the total score and the scores of feeling of non-well being, pain and shortness of breath of ESAS in the acupuncture group (the high-dose acupuncture group combined with the low-dose acupuncture group) were lower than the control group (P<0.05). CONCLUSION Acupuncture shows promising effect in controlling symptom burden during adjuvant chemotherapy in gastric cancer patients after gastrectomy.
Humans ; Acupuncture Points ; Stomach Neoplasms/surgery* ; Acupuncture Therapy ; Gastrectomy/adverse effects* ; Chemotherapy, Adjuvant

Objective: To investigate the value of stool-based methylated SDC2 test in physical examination population for the screening of colorectal neoplasms. Methods: Using the prospective cohort study method, from December 2020 to November 2021, 2 107 participants from the First People's Hospital of Xiushui County, Jiangxi Province were enrolled, consisted of 1 012 males and 1 094 females, aged 20-90 years with the median age of 49 years old. Fresh stool samples were collected and SDC2 DNA methylation tests were carried out as the primary screening method. The participants with positive results were recommended to undergo colonoscopy, and those who were negative were followed up by telephone. The positive rate of screening, the compliance of colonoscopy, and the detection of colorectal lesions were analyzed by chi-square test. Combined the follow-up results of negative subjects, the value of SDC2 DNA methylation test for the screening of colorectal neoplasms was evaluated. Results: Among the 2 107 participants, 2 106 completed the SDC2 methylation test. 113 participants (5.4%) were positive. The positive rate of primary screening increased with age significantly (χ²=32.135, P<0.001). Out of 113 cases, 72 (63.7%) underwent colonoscopy examinations. Finally, 3 (4.2%) cases of colorectal cancer, 12 (16.7%) cases of advanced adenoma, 31 (43.1%) cases of non-advanced adenoma, and 16 (22.2%) cases of non-adenomatous polyp were detected. The positive predictive value (PPV) of stool-based SDC2 DNA methylation test for intestinal lesions and colorectal neoplasms were 86.1% and 63.9%, respectively. Among the 1 374 follow-up participants, the negative predictive value (NPV) of this test for intestinal lesions and colorectal neoplasms were 97.7% and 99.4%, respectively. Conclusion: Primary stool-based SDC2 DNA methylation test and subsequent colonoscopy examination can effectively find colorectal neoplasms. This strategy may be a potential tool for the screening of colorectal neoplasms in general risk population.
Male ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Prospective Studies ; Early Detection of Cancer/methods* ; Colorectal Neoplasms/diagnosis* ; Mass Screening/methods* ; Feces ; DNA Methylation ; Colonoscopy ; Physical Examination ; Syndecan-2/genetics*