Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

ObjectiveTo comprehensively evaluate the clinical value of Feilike mixture and provide a basis for the allocation of medical resources， rational drug use， and hospital procurement and supply of Chinese patent medicines. MethodWith the data from available studies and provided by drug manufacturers， the methods of evidence-based medicine， pharmacoeconomics， and health technology assessment were employed to construct a multi-criteria decision-making analysis framework from the "6+1" dimensions of safety， effectiveness， economy， innovation， suitability， accessibility， and characteristics of traditional Chinese medicine （TCM）. The clinical evidence and value evaluation software of Chinese patent medicine， CSCv2.0， was used to comprehensively evaluate the clinical value of Feilike mixture. ResultBased on the existing clinical evidence， the following results were obtained. ① Safety： Multi-sources of evidence showed that Feilike mixture had little known risk and sufficient evidence， with the safety rated as grade A， which indicated good safety. ② Effectiveness： The systematic review and Meta-analysis showed that Feilike mixture combined with conventional Western medicine in the treatment of bronchitis shortened the time to disappearance of cough compared with conventional Western medicine alone， with the evidence rated as grade B by the Grading of Recommendations Assessment， Development， and Evaluations （GRADE） system， which indicated high effectiveness. ③ Economy： From the perspective of health system， Feilike mixture combined with conventional Western medicine was more economical than conventional Western medicine alone， and the quality evaluation of pharmacoeconomics rated the economy as grade B. ④ Innovation： Feilike mixture combined with conventional Western medicine improved the clinical treatment effect and had innovation advantages compared with similar drugs. From the aspects of cultivation， identification of medicinal materials， and production， the sufficient supply and safety of medicinal materials can be ensured for Feilike mixture. This medicine was rated as grade B in terms of the medicinal material quality， preparation technology， and patents， which indicated good innovation. ⑤ Suitability： According to the results of the questionnaire survey， the usage of Feilike mixture was easy to be mastered and accepted by doctors and nurses， without special administration time， complex personalized treatment， and special technical and management requirements. It is convenient for patients to use， with convenient supply and storage， and weak influences of policy， publicity， and drug information. Therefore， the suitability of Feilike mixture was rated as grade B. ⑥ Accessibility： Among the similar Chinese patent medicines， Feilike mixture had a moderate price， high production capacity， wide sales coverage， wide coverage of hospitals， sustainable supply of medicinal materials， and low costs of treatment for acute bronchitis， with the accessibility rated as grade A. ⑦ TCM characteristics： Feilike mixture is composed of Scutellariae Radix， Peucedani Radix， Stemonae Radix， Gentianae Rhodanthae Herba， Scleromitrion diffusum， Firmiana platanifolia Radix， and Aster ageratoides， with reasonable compatibility. This formula is derived from the medical experience of Miao ethnic group， with rich experience in human use and the TCM characteristics rated as grade B. According to the evaluation results in the "6+1" dimensions， Feilike mixture was evaluated as class B， with a high clinical value. ConclusionAccording to the existing clinical evidence， compared with conventional Western medicine alone， Feilike mixture combined with conventional Western medicine demonstrates a high clinical value and prominent TCM characteristics in the treatment of acute bronchitis with phlegm-heat invading lung. It is suggested that it should be translated into the basic clinical drug management policy results according to the conditions.

The repair and reconstruction of long ureteral defects is a technical challenge faced by urologists. The ileal ureter replacement is currently the main surgical method for treating long segment ureteral defects. After the ileal ureter replacement surgery, mucin 2 (MUC2) and mucin 3 (MUC3), which are the main functional components of ileal mucus, continue to be strongly expressed. In addition, the expression of MUC2 gene after surgery is not limited to goblet cells, but can even be expressed in absorption cells of the ileum, ultimately leading to a large amount of mucin synthesis and mucus secretion. Mucus can cause many complications such as obstruction and infection, seriously affecting the treatment effect. At present, the industry has tried various methods to reduce the secretion of mucus and related complications after ileal ureteral replacement surgery, such as cutting the ileum to reduce mucosal area and mucosal exfoliation to reduce mucus production, and has achieved certain results. This article provides a review of research progress on the types, molecular mechanisms, and solutions of mucus related complications after ileal ureteral replacement surgery.

Objective:To develop and evaluate a medical experience assessment scale for debridement and dressing change in chronic wound patients in China, and to provide a reference for improving hospital service quality.Methods:Based on the framework of hospital consumer assessment of healthcare providers and systems survey (HCAHPS) in the United States, a preliminary draft of the scale was formed through a literature review and qualitative interviews with 12 chronic wound patients (7 males and 5 females aged 58.1±12.3 years). Five experts were invited for content validity testing, and 191 chronic wound patients (111 males and 80 females aged 53.5±19.1 years) were selected to evaluate the internal consistency reliability, half reliability, retest reliability, and structural validity of the scale.Results:The Chronic Wound Patient Debridement and Dressing Experience Scale covered 5 dimensions with 30 sub-items and 2 comprehensive evaluation items, including demand response, good and friendly communication, professional trust, optimization of the medical treatment process, and encouragement of patient participation. The scale Cronbach′s α coefficient was 0.967 and ranged from 0.890 to 0.962 for each dimension. The overall retest reliability of the scale was 0.940 and ranged from 0.895 to 0.940 for each dimension. The overall half reliability of the scale was 0.923 and ranged from 0.834 to 0.935 for each dimension. 5 factors were extracted, with a cumulative variance contribution rate of 82.061%.Conclusions:Based on the HCAHPS framework in the United States, the Chronic Wound Debridement and Dressing Experience Scale developed has high reliability and validity, and can be used to evaluate the dressing change experience of patients with chronic wounds. It has clinical practice significance for dressing change in chronic wounds.

Objective: To investigate the characteristics of sleep-related respiratory events in normal children and to provide normal polysomnographic parameters for diagnosing sleep-disordered breathing in children. Methods: Normal subjects between 3 and 14 years old were enrolled from 1 July 2014 to 31 December 2015 and the subjects received overnight polysomnography at the sleep center of our hospital. They were children of our hospital employees or were recruited from the communities who did not have sleep and respiratory disorders. The children were divided into preschool group (3-5 years) and school-age group (6-14 years). Apnea index (AI), obstructive apnea index (OAI), central apnea index (CAI), and mixed apnea index (MAI) were compared between the two groups. Data for continuous variables that showed normal distribution were expressed as ±s. M(P₂₅, P₇₅) were used when data were not normally distributed. Continuous variables that showed normal distribution were compared by using an independent-sample t-test. Wilcoxon-test was performed when data exhibited non-normal distribution. Differences in categorical data were tested with Chi-square test. Pearson correlation test was applied for the correlation analysis. P<0.05 was considered statistically significant. Results: A total of 115 normal children took part in the study including 40 in preschool group and 75 in school-age group. Children in both groups had a few sleep apnea events, most of which were central apneas, accounting for 80% and 70% of the total respiratory events respectively. Central apnea index in preschool children were significantly higher than that of school-age children (P<0.001), with median of 0.6 times/h and 0.1 times/h, respectively. Median OAI of both groups were 0.0 times/h without significant difference (P=0.748). Obstructive apnea events occurred mainly in the supine position in both groups. Conclusions Normal children may have a few apnea events in sleep that were predominantly central apnea. CAI of preschool children is significantly higher than that of school-age children. Obstructive sleep apnea is rare in normal children, and sleep apnea occurs mainly in the supine position.

Objective To observe the effect of aerobic exercise of different intensities on type Ⅱ collagen,glycosaminoglycan (GAG) and chondrocyte apoptosis in rabbits modeling knee osteoarthritis (OA),so as to explore the preventive effect and its possible mechanism.Methods Twenty healthy New Zealand white rabbits were randomly divided into Groups A,B,C and D,each of 5.Group A was allowed free activity in a cage for 9 weeks.Group B was allowed free activity for 4 weeks,then an OA model was established using papain and confirmed via MRI 1 week later,Another 4 weeks of free activity were then allowed.Groups C and group D were given running training for 20 minutes a day at 0.5 km/h,3 times a week,and then 20 minutes a day at 1.5 km/h,5 days a week on a treadmill for 4 weeks.Nine weeks later,all 4 groups of rabbits were killed and the articular cartilage damage of each group was compared using Mankin scoring,and expression of type Ⅱ collagen,GAG content and chondrocyte apoptosis in the cartilage.Results After the intervention,the average Mankin score,expression of type Ⅱ collagen and GAG content of groups B,C and D were significantly lower than those of group A,and all of those values in group B were significantly lower than those of group D.After 9 weeks the chondrocyte apoptosis rate of group A was significantly lower than that of the other groups,and that of groups C and D was significantly lower than that of group B.Conclusion Aerobic exercise may prevent knee articular cartilage degeneration through inhibiting reduction in the amount of type Ⅱ collagen and GAG in the cartilage matrix.It may be related to decreasing the chondrocyte apoptosis.

Objective To analyze the research directions and research status of main academic teams of TCM treatment for ulcerative colitis in the recent 15 years.Methods Articles about TCM treatment for ulcerative colitis from Jan. 2000 to Dec. 2015 in CNKI were searched. Articles were screened by inclusion and exclusion criteria, and then publication time and research institutes were under metrology analysis. According to Price Law and comprehensive indexes, core authors were indentified. The NetDraw2.118 social network was applied to establish author co-occurrence matrix, build core author relationship network and screen academic teams. Combined with typical articles, main research fields and research status of main academic teams were analyzed.Results3658 were included from 6365 articles. 33 core authors in the filed of TCM treatment for ulcerative colitis were identified, belonging to 5 academic teams with relatively higher academic influence: Wu Huangan team, Shenhong team, Wang Hongxia team, Liu Yihua team and Zhang Yansheng team. Each team proposed unique diagnosis and treatment methods.Conclusion Academic teams of TCM treatment for ulcerative colitis have inherited and promoted TCM theories and formed unique academic system in clinical practice and research.

BACKGROUND:There are numerous clinical studies on comparing absorbable internal fixation system and titanium metal internal fixation system in maxilofacial fractures; however, the systematic reviews and Meta-analysis in this field are rare. OBJECTIVE:To compare the clinical effect of absorbable internal fixation system and titanium internal fixation system in maxilofacial fractures through systematic review and Meta-analysis. MATERIALS AND METHODS:The randomized controled trials and controled clinical trials regarding the application of absorbable internal fixation system and titanium internal fixation system in maxilofacial fractures were electronicaly retrieved from Medline, Embase, the Cochrane Central Register of Controled Trials, China Biology Medicine disc, and China Academic Journal Network Publishing Database using the keywords. Meta-analysis was conducted using Revman 5.3 software. RESULTS AND CONCLUSION:Thirteen clinical studies were included, and totaly 1 718 patients were involved. The Meta-analysis results showed that the removal rate of implants in the absorbable internal fixation system group was significantly lower than that in the titanium internal fixation group (P=0.000 2); there were no significant differences in the healing rate of fracture I stage, the incidence of insufficient fixation in fracture site and the incidence of long-term complications between these two groups. These results demonstrate that the efficiency and safety of absorbable internal fixation system in maxillofacial fracture is satisfactory, and can reduce the proportion of secondary surgical removal of the implant. More randomized controlled trials should be conducted to confirm this conclusion.

Objective To evaluate the effectiveness and safety of needle-knife fistulotomy (NKF)for difficult cannulation during endoscopic retrograde cholangiopancreatography (ERCP). Methods Data of patients, who received NKF on the back of major papilla when bile duct could not be accessed by conventional cannulation and/or other pre-cut methods during ERCP, were retrospectively reviewed. The success rate of deep cannulation and its complications were observed and analyzed. Results NKF was performed in 108patients due to difficult cannulation, which succeeded in 97 (91.2%) in access to the bile duct and failed in 11 patients with malignant biliary strictures. The failure rate in patients with distal malignant obstruction was higher (25. 8%, 8/31) than those with proximal lesions (5.3%, 3/57) (P = 0. 014, χ2 = 5. 983).Post-ERCP pancreatitis occurred in 5 cases (4. 6%), with the incidence significantly higher in NKF-failure group (18. 2%, 2/11) than that in NKF-suocess group (3.1% ,3/97) (P = 0. 006, χ2 = 7.418). Intestinal perforation occurred in 1 patient and cholangitis developed in 4 others, which all recovered after conservative managements. Conclusion NKF for difficult cannulations in ERCP is safe and effective, especially in hands of experienced operators, but cannulation success rate is relatively low in distal malignant biliary obstruction.

Objective To investigate the feasibility of applying nanotechnology against M.tuberculosis growth.Methods Chitosan-antisense ODN nanoparticles were prepared by complex coacervation method.Varied amount of ODNs and chitosanODN nanoparticles were added to the cultures and the growth of the bacilli was monitored.Results The nanoparticles were composed of(35.6±0.9)% ODN and(64.4±0.9)% chitosan.Compared to the free ODN,antisense nanopartilces were more effective in inhibiting the proliferation of M.tuberculosis.Antisense nanoparticles decreased growth by(2.8±0.1)CFU/ml at concentration of 4/μmol/L.Conclusion Chitosan-ODN nanoparticles were more effective in inhibiting the growth of M.tuberculosis than free ODN.