Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24⁺), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.
Humans ; Spleen ; Irritable Bowel Syndrome/drug therapy* ; Quality of Life ; Yang Deficiency/drug therapy* ; Kidney ; Diarrhea

Animals ; Schistosoma japonicum ; Colitis, Ulcerative

OBJECTIVE: To analyze dynamic electromyography characteristics and related factors of lumbar back muscle activity in patients with lumbar disc herniation, and to clarify the clinical significance of dynamic electromyography in the diagnosis and treatment of patients with lumbar disc herniation(LDH). METHODS: From September 2014 to March 2021, 40 patients with lumbar disc herniation(LDH group) were detected by surface electromyography telemeter. There were 14 males and 26 females, aged from 20 to 61 years old, with an average of(40.68±10.56) years old, the course of illness was from 1 to 120 months, with an average of (17.75±27.56) months. In addition, 12 normal people were recruited as the control group. There were 2 males and 10 females. The age ranged from 24 to 53 years old, with an average of(36.50±10.30) years old. All subjects were subjected to dynamic electromyographic tests of the subthoracic erector spinae, lumbar erector spinae, and multifidus muscles during static standing and trunk flexion and extension. Compare the EMG activity data (average EMG amplitude, median frequency, original EMG graph) of the tested muscles between patients with lumbar disc herniation and normal people, and analyze the correlation between the general data of patients with lumbar disc herniation and the tested muscle EMG data. RESULTS: When standing still, the average electromyographic amplitude of the erector spinal muscle of the right and left thoracic segments of the subjects in the LDH group increased compared with the control group, and the difference was significant(P<0.05). In the trunk flexion and extension, the average electromyographic amplitude of the right and left proximal thoracic erector spinae, the right left lumbar erector spinae, and the right left multifidus muscle of the subjects in the LDH group are all larger than the control group, and the difference was significant(P<0.05). In the trunk flexion and extension, the median frequencies of the right left proximal thoracic erector spinae、the right left lumbar erector spinae, and the right left multifidus muscle of the subjects in the LDH group were all larger than the normal control group, and the difference was significant (P<0.05). During trunk flexion and extension, the original electromyographic patterns of subjects in the LDH group were significantly different from those in the control group. During the maintenance of the maximum trunk flexion of the subjects in the LDH group, there was a high level of electromyographic activity of the lower back muscles, and the electromyographic static signals that should appear regularly in the original signal could not be distinguished. When the trunk was flexed and extended, had gender, age, weight and height of subjects in the LDH group were not significantly correlated with the average EMG amplitude and median frequency of bilateral proximal thoracic, lumbar erector spinae and bilateral multifidus muscles respectively(P>0.05). CONCLUSION Patients with lumbar disc herniation have characteristic surface EMG changes in the back muscles that are different from those of normal people. These features can more objectively reflect the patient's muscle condition and can be an effective indicator for the diagnosis and treatment effect evaluation of patients with lumbar disc herniation. It can be seen that surface electromyography is not only a detection method, it can be considered in the routine diagnosis and treatment plan of LDH to guide clinical work.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Electromyography ; Intervertebral Disc Displacement/therapy* ; Lumbar Vertebrae ; Paraspinal Muscles ; Range of Motion, Articular/physiology* ; Muscle, Skeletal

At present, heavy ion is an ideal radiation for cancer treatment, and carbon ion is used in the treatment of many kinds of cancer due to its higher relative biological effect value. In 2019, Wuwei heavy ion center built the first medical heavy ion accelerator-carbon ion radiotherapy system in China, and obtained the registration license from the National Medical Products Administration, and officially received cancer patients in March 2020. This study introduced the development and application of the first carbon ion radiotherapy system in China.
Carbon ; China ; Heavy Ion Radiotherapy ; Heavy Ions ; Humans ; Neoplasms/radiotherapy*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors. METHODS: DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation. RESULTS: Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors. CONCLUSION The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.
Adenoma, Oxyphilic/genetics* ; Biomarkers, Tumor/metabolism* ; Cell Adhesion Molecules/metabolism* ; DNA Methylation ; GPI-Linked Proteins/metabolism* ; Humans ; Hyaluronoglucosaminidase/metabolism* ; Immunohistochemistry ; Middle Aged ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.
Animals ; Deer/metabolism* ; Gelatin ; Glycosylation ; Hydroxylation ; Lysine/metabolism* ; Protein Processing, Post-Translational ; Tandem Mass Spectrometry

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.