Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

The cGAS-STING signaling pathway plays a crucial role in innate immunity,forming a monitoring system for tissue injury and pathogen invasion.Recent studies have found that the cGAS-STING signaling pathway may mediate a vari-ety of pathological processes in eyes and participate in the occurrence and development of inflammatory,degenerative eye diseases and ocular tumors,such as keratitis,age-related macular degeneration,diabetic retinopathy,and uveal melano-ma.This review aims to summarize the role of the cGAS-STING signaling pathway in eye diseases and elucidate the poten-tial molecular mechanisms of the cGAS-STING signaling pathway in eye diseases,so as to provide innovative approaches to the treatment of eye diseases.

Objective:To explore the molecular mechanism of the effect of the histone methylase zeste gene enhancer homolog 2 (EZH2) on the proliferation and apoptosis of human hypertrophic cardiomyocytes AC16.Methods:The AC16 hypertrophic cardiomyocyte model was constructed by adding angiotensin Ⅱ to the AC16 cell culture medium. The cells were divided into four groups, including the blank control group, the angiotensin Ⅱ group, the empty vector + angiotensin Ⅱ group, and the EZH2 overexpression + angiotensin Ⅱ group. The expression levels of EZH2 and brain natriuretic peptide ( BNP) genes were measured using fluorescent quantitative PCR. The EZH2, trimethylation of lysine at position 27 of histone H3 (H3K27me3), and BNP proteins expression were detected by Western Blot. The MTS method was used to detect the proliferation of AC16 cell. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of AC16 cell. Results:Compared with the blank control group, the expression levels of EZH2 and H3K27me3 in the angiotensin Ⅱ group were decreased, the expression level of BNP was increased, cell proliferation was decreased, and apoptosis was increased (all P < 0.001). Compared with the empty vector + angiotensin Ⅱ group, the expression levels of EZH2 and H3K27me3 in the EZH2 overexpression + angiotensin Ⅱ group were increased, the expression level of BNP was decreased, the cell proliferation level was increased, and the apoptosis level was decreased (all P < 0.001). There was no significant difference between the angiotensin Ⅱ group and the empty vector + angiotensin Ⅱ group (all P > 0.05). Conclusions:Histone methylase EZH2 has an effect on the proliferation and apoptosis of AC16 cell, providing a reference for the treatment of myocardial hypertrophy and revealing the exact pathogenesis of myocardial hypertrophy.

Cold atmospheric plasma (CAP), a redox modulation tool, is capable of inhibiting a wide spectrum of cancers and has thus been proposed as an emerging onco-therapy. However, with incremental successes consecutively reported on the anticancer efficacy of CAP, no consensus has been made on the types of tumours sensitive to CAP due to the different intrinsic characteristics of the cells and the heterogeneous design of CAP devices and their parameter configurations. These factors have substantially hindered the clinical use of CAP as an oncotherapy. It is thus imperative to clarify the tumour types responsive to CAP, the experimental models available for CAP-associated investigations, CAP administration strategies and the mechanisms by which CAP exerts its anticancer effects with the aim of identifying important yet less studied areas to accelerate the process of translating CAP into clinical use and fostering the field of plasma oncology.

Aspergillus niger is an important industrial strain which has been widely used for production of enzymes and organic acids. Genome modification of A. niger is required to further improve its potential for industrial production. CRISPR/Cas9 is a widely used genome editing technique for A. niger, but its application in industrial strains modification is hampered by the need for integration of a selection marker into the genome or low gene editing efficiency. Here we report a highly efficient marker-free genome editing method for A. niger based on CRISPR/Cas9 technique. Firstly, we constructed a co-expression plasmid of sgRNA and Cas9 with a replication initiation region fragment AMA1 (autonomously maintained in Aspergillus) by using 5S rRNA promoter which improved sgRNA expression. Meanwhile, a strain deficient in non-homologous end-joining (NHEJ) was developed by knocking out the kusA gene. Finally, we took advantage of the instability of plasmid containing AMA1 fragment to cure the co-expression plasmid containing sgRNA and Cas9 through passaging on non-selective plate. With this method, the efficiency of gene editing reached 100% when using maker-free donor DNA with a short homologous arm of 20 bp. This method may facilitate investigation of gene functions and construction of cell factories for A. niger.
Gene Editing ; Aspergillus niger/genetics* ; CRISPR-Cas Systems/genetics* ; Plasmids/genetics*

Objective:To analyze the correlation factors between peripapillary duodenal diverticulum (PDD) and choledochectasia by CT scan.Methods:The clinical data of 220 patients with duodenal diverticulum detected by multi-slice spiral CT scan and confirmed by gastrointestinal angiography or endoscopic retrograde cholangiopancreatography (ERCP) in Dahua Hospital, Xuhui District of Shanghai City were retrospectively analyzed. The correlation of the PDD, the contact of common bile duct (CBD), length of contact and exudation with choledochectasia in patients with PDD were analyzed.Results:A total of 236 duodenal diverticulum were found in 220 patients. Among them, there were 152 PDD, 41 diverticulum located superior to the duodenal papilla, 28 diverticulum located inferior to the duodenal papilla, 3 diverticulum located lateral to the duodenal papilla, and 12 diverticulumlocated in the horizontal portion. The incidence of choledochectasia in patients with PDD contacted with CBD was significantly higher than that in patients with PDD not contacted with CBD: 59.35% (73/123) vs. 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in patients with contact length of PDD and CBD ≥1.5 cm was significantly higher than that in patients without contact of PDD and CBD and patients with contact length of PDD and CBD <1.5 cm: 82.43% (61/74) vs. 24.49% (12/49) and 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in PDD patients with exudation was significantly higher than that in PDD patients without exudation: 10/11 vs. 52.48% (74/141), and there was statistical difference ( P<0.05). Conclusions:The patients with contact length of PDD and CBD ≥1.5 cm and patients with PDD combined with exudation could be prone to choledochectasia.

Objective:To explore the clinical effects of the "Disease-Characteristics" project in improving the nursing quality of patients with diabetic retinopathy (DR) .Methods:Based on the content framework of "Disease-Characteristics", authoritative data of UpToTate and various guidelines were transformed into evidence for clinical application through the steps of evidence-based nursing, and a standardized "Disease-Characteristics" project for DR patients was constructed. Convenience sampling was adopted to select nurses who worked in the Shanghai Eye Hospital and the Ophthalmology Department of Shanghai First People's Hospital from January 1, 2018 to June 30, 2019 as research nurses. Convenience sampling was used to select 223 DR patients admitted to the two hospitals from October 30, 2018 to January 31, 2019 (before implementation) as the control group, and 261 patients with DR admitted from February 1, 2019 to April 30, 2019 (after implementation) as the observation group. We observed and compared indicators such as the correct rate of nurses' assessment of each key link of DR patients before and after implementation, the awareness rate of patients' DR-related knowledge, and the incidence of postoperative complications of patients.Results:After the implementation, the scores of the nurses in the assessment of each key link of DR patients increased from (90.36±1.16) to (96.72±1.13) , and the difference was statistically significant ( t=52.990, P<0.05) . The disease-related knowledge score of DR patients increased from (74.330±12.154) to (78.386±10.094) , and the difference was statistically significant ( t=4.010, P<0.05) . Postoperative complications such as persistent high intraocular pressure, vitreous rebleeding, inflammatory edema and diplopia were improved, and the differences were statistically significant ( χ2=7.131, 5.618, 5.788, 6.128; P<0.05) . Conclusions:The "Disease-Characteristics" project plan based on the best evidence has a certain significance for improving the nursing quality of DR and the prognosis of patients.

Objective:On the basis of introducing and piloting long-term care insurance services and providing home care for older adults with disabilities in Suzhou, this paper aims to explore the working experience of home caregivers in the caring environment, understand their difficulties and issues, explore their true feelings and the relevant causes, and to draw lessons from their experience, providing constructive suggestions for the establishment of caregivers as well as policy recommendations for the government.Methods:The qualitative research method was used to collect the field experience data of 9 home caregivers in the caring environemnt through observation and semi-structured interview. Colaizzi phenomenological analysis was used to process and analyze the data.Result:1. Heavy workload and lack of incentive mechanism; 2. Care experience is diverse, with a sense of achievement and happiness, but lack of family′s trust and identification; 3. Professional trainings and peer support are needed.Conclusion:1. Improving the working environment of caregivers and reducing the burden of care; 2.Improve the employment treatment of home care workers, and actively improve the relevant incentive mechanism;3. Paying attention to the emotional experience of caregivers and helping them adapt to their role; 4.Standardize professional knowledge and skills training, provide risk assessment tools, and improve the quality of care.

Objective: To explore the effectiveness of collaborative care model-based continuous nursing on the postpartum posttraumatic stress disorder(PPTSD), to provide reference for postpartum clinical nursing. Methods: A total of 100 cases of postpartum puerpera in Beijing Luhe Hospital of Capital Medical University were assigned to the intervention group and the control group according to the random number table method with 50 cases each. In the control group, patients received continuous nursing, however, collaboration care model-based continuous nursing care was carried out in the intervention group. The PPTSD status and psychological resilience between the two groups was assessed by Posttraumatic stress Checklist-Civilian version (PCL-C) and Connor-Davidson Resilience Scale (CD-RISC), respevtively. Results: Before intervention, symptoms scores and total scores of PCL-C and CD-RISC between the two group was no statistical difference (P>0.05). After intervention, the scores of increased arousal symptoms (7.22±1.09), avoidance/numbing (9.77±2.41), re-experiencing symptoms (5.66±1.17) and PCL-C total scores (22.64±3.02) were significantly decreased in the intervention group compared to the control group (8.32 ± 1.05), (11.46 ± 2.87), (6.36 ± 1.25), (26.14 ± 3.27), and there were significant differences between the two groups (t=2.899-5.559, all P<0.01). However, the scores of tenacity (24.90 ± 4.83), strength (14.91 ± 2.25), optimism (7.18 ± 1.61) symptoms and CD-RISC total scores (46.99 ± 6.30) were remakedly increased in the intervention group compared to the control group (23.22 ± 2.69), (13.61 ± 1.75), (6.14 ± 0.91), (42.97 ± 3.30), there were significant differences between the two groups (t=2.154-4.011, P<0.05 or 0.01). Conclusions Collaboration care model-based continuous nursing care can promote the psychological resilience and alliviate PPTSD.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.