Tryptophan metabolism plays an important role in immunometabolism in sepsis,and the expression of indoleamine 2,3-dioxygenase 1(IDO1),the key enzyme of tryptophan metabolism,is up-regulated during sepsis.This study was designed to construct IDO1 gene knockout THP-1 cell line using CRISPR/Cas9,and to provide a cell model for studying the role of IDO1 in macrophage function.Three gRNAs were designed for the IDO1 gene,and inserted into YKO-Lentiviral gRNA plasmid respectively to construct IDO1-gRNA recombinant plasmid,which then confirmed by restriction enzyme digestion and sequencing,and packaged as Lenti-IDO1-gRNA lentivirus.THP-1 cells were infected with Cas9 lentivirus to construct a THP-1 Cas9 cell line stably expressing Cas9 protein.Then THP-1 Cas9 cells were infected with the Lenti-IDO1-gRNA lentivirus for IDO1 gene knockout,and the monoclonal cell lines were screened by limited dilution method.The efficiency of IDO1 knockout was identified by T7E1 digestion test,PCR product sequencing and Western blotting.The proliferative activity of THP-1 cells was detected by CCK8 assay;the expression of CD11b,CD68 and CD 14 in THP-1 macrophages were detected by flow cytometry;and the phagocytic function of THP-1 macrophages was detected by neutral phagocytosis test.T7E1 restriction enzyme digestion results showed that all the three gRNAs could effectively edit IDO1 gene,and gRNA2 had the highest editing efficiency.Sequencing of PCR products showed that IDO1 gene was mutated in three THP-1 IDO 1-KO monoclonal cell lines,and Western blot result showed that IDO1 protein was not expressed,suggesting THP-1 IDO1-KO cells were successfully constructed.CCK-8 proliferation assay showed that IDO1 gene knockout could inhibit the proliferation of THP-1 cells.Flow cytometry showed that IDO1 gene knockout down-regulated the expression of CD1 1b and CD68 in THP-1 macrophages,while up-regulated the expression of CD 14.The results of neutral red phagocytosis test showed that IDO1 gene knockout promoted the phagocytosis of macrophages.In conclusion,the IDO1 gene knockout THP-1 cell line has successfully constructed by CRISPR-Cas9,and IDO1 plays an important role in regulating the proliferation activity and differentiation of THP-1 cells,as well as the phagocytic function of THP-1 macrophages.

Objective:To investigate the clinical effectiveness and significance of special fixing cartilaginous support structure on nasal tip to prevent and correct alar rim retraction.Methods:Special shaped tip extension support structure was composed of two parts of type Ⅲ of septum extension graft (SEG) and two pieces of wedge graft fixed on either side of the cephalic end near the top of support structure. After the alar cartilage vault was fixed to the nasal tip cartilage support structure, the lower lateral cartilage (LLC) cephalic was fixed to both sides of this nasal tip support structure. The LLC received support from the cartilaginous support structure to counter and correct the lower lateral cartilage cephalic retraction. From January 2017 to January 2020, this surgical procedure was used in 34 patients (aged from 20 to 46 years, with mean 32.6 years) with rhinoplasty who had a nasal tip support structure but still had a space between the LLC and the stent intraoperativly. Preoperativly, 4 cases had normal relation of alar columella and alar rim, 18 cases had mild alar rim retraction, and 12 cases had moderate alar rim retraction. The patients were followed up for 6 to 18 months to observe the correction effect and patient satisfaction.Results:Among the 34 patients, 8 patients received alar edge graft, 2 patients received lateral foot support graft, and 2 patients received alar rim graft combined with lateral foot support graft. All patients were followed up for 6-18 months, 30 patients with alar rim retraction were completely corrected, and 4 patients with normal alar and nasal columella relationship did not have alar rim retraction after surgery. No complications such as infection, necrosis, contracture or respiratory dysfunction were found in all patients. 28 cases (82.4%) were very satisfied; 6 cases (17.6%) were satisfied; the satisfactory rate was 100%.Conclusions:The special shaped nasal tip cartilage support structure combined with type Ⅲ SEG and its cephalic wedge grafts could achieve satisfactory clinical results in the prevention and correction of alar rim retraction.

Objective:To explore the feasibility and advantages of integrated prosthesis of expanded polytetra-fluoroethylene (e-PTFE) in eyebrow arch augmentation.Methods:The clinical data of 45 patients with low or flat brow arch and glabellar zone from June 2019 to October 2020 in Chengdu High-tech Zone Xinyuerong Medical Aesthetic Clinic were analyzed retrospectively, in which it included 45 women, whose ages ranged from 20 to 39 years with average 29.8 years. Forty-three cases underwent primary surgery, and 2 cases underwent repair. The e-PTFE was sculpted to be personalized integrated prosthesis according to the shape of the patient's eyebrow arch and glabellar zone. The incision was designed on the medial and lateral sides of the lower margin of the bilateral eyebrow to avoid the supraorbital foramen, and the lacunae were striped under the frontal periosteum, and the two sides were connected to cover the glabellar zone and inverted triangle area between the eyebrows. The carved e-PTFE was implanted into one side and pulled out from the other side. The prosthesis was smoothed by Venn pliers of the ventral and dorsal sides.Results:The 45 patients in this group were followed up for 6-18 months. The incisions of all the patients were healed Ⅰ/A, and the scar of the incisions was concealed. Slight scalp numbness occurred in 4 patients and returned to normal 3 months later. The prosthesis in the glabellar zone appeared in 1 case 3 months after operation and returned to normal after reoperation. The symmetry, radian, fullness, convexity and tactility of bilateral eyebrow arch were all satisfactory in 45 cases. 39 cases were very satisfied, accounting for 86.7%; 6 cases (13.3%) were satisfactory. The sagittal distance of the anterior surface of the cornea to the soft tissues overlying the supraorbital rims was (2.02±1.72) mm preoperatively and (6.5±1.19) mm in the last follow-up. The difference was statistically significant ( t=14.49, P<0.01). Conclusions:This design of integral e-PTFE in eyebrow arch augmentation is safe, effective and easy to operate. It can significantly increase the bony beauty and stereoscopic sense of the eyebrow arch and glabellar zone, effectively deepen the eye socket, improve the eye protrusion, and reduce the risk of asymmetry and prosthesis displacement, and therefore it is one of the ideal methods for eyebrow arch augmentation.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.
Animals ; Collagen/metabolism* ; Wound Healing ; Tissue Engineering ; Tissue Scaffolds ; Cosmetics ; Mammals/metabolism*

Anterior cervical fusion surgery is the first choice for spine surgeons in the treatment of cervical spine diseases. It has significant effects in treating cervical degenerative diseases, trauma and tumors and other cervical diseases. In anterior cervical fusion, it is necessary to use a distractor to properly distract the intervertebral space, so as to fully expose and relieve the compressive factors, restore the physiological height, curvature and stability of the lesion segment, and achieve the best surgical effect. However, there is currently no consensus on the standard distraction height for the intervertebral space during anterior cervical surgery. This article reviewsed the progress of intervertebral space height in anterior cervical fusion from three dimensions:the relationship between intervertebral space height and cervical disc degeneration mechanism, the selection of intervertebral space height during operation, the recovery of intervertebral space height and the postoperative effect, so as to provide theoretical basis and reference for spinal surgeons when performing intervertebral distraction during operation.
Cervical Vertebrae/surgery* ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration ; Neck ; Spinal Fusion ; Treatment Outcome

OBJECTIVE: To observe the effect of horizontal penetration needling at vertigo auditory area and balance area on residual dizziness after successful repositioning maneuver in patients with benign paroxysmal positional vertigo (BPPV). METHODS: Sixty-six patients with residual dizziness after successful repositioning maneuver for BPPV were randomly divided into an observation group (34 cases, 1 case dropped off) and a control group (32 cases, 2 cases dropped off). The patients in the observation group were treated with horizontal penetration needling at vertigo auditory area and balance area, once every other day; three times were taken as a course of treatment, and two courses of treatment were given. The patients in the control group received no acupuncture and medication. The dizziness handicap inventory (DHI) and visual analogue scale (VAS) scores were observed before treatment and after 1 and 2 courses of treatment. RESULTS: Except for the emotional score of DHI in the control group after 1 course of treatment, the sub item scores and total scores of DHI and VAS scores in the two groups after treatment were lower than those before treatment ( CONCLUSION Whether acupuncture or not, residual dizziness after repositioning maneuver for BPPV can be relieved within 2 weeks; horizontal penetration needling at vertigo auditory area and balance area could improve dizziness symptoms and shorten the course of disease.
Benign Paroxysmal Positional Vertigo/therapy* ; Dizziness/therapy* ; Humans ; Patient Positioning ; Vascular Surgical Procedures

Animals ; Bleomycin ; Epithelial-Mesenchymal Transition ; Lung ; Male ; Pulmonary Fibrosis/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Simvastatin/pharmacology*

Objective:To investigate the effectiveness of a modified upper lip lifting technique with retaining the nasal columellar base incision.Methods:From Jun. 2019 to Jun. 2020, 24 cosmetic patients (aged from 18 to 36 years, with mean 26.5 years) underwent upper lip lifting with skin flap resection of bilateral upper lip flaps and retained the nasal columellar base in Chengdu High-Tech Zone Xinyuerong Medical Aesthetic Clinic. These factors were analyzed, including postoperative complications, improvement of nasolabial angle, effectiveness of upper lip lifting and overall satisfaction.Results:In the 24 patients, 2 patients had numbness in the upper lip after surgery, and returned to normal after 4 months. The concealed scar was effective to improve the linear scar and scar contracture of traditional upper lip lifting. All patients were followed up for 3 months to 1 year. The satisfactory lifting effectiveness was obtained in 24 cases. As for overall satisfaction, 22 cases were very satisfied (91.7%) and 2 cases were satisfied (8.3%).Conclusions:This upper lip lifting surgical procedure of upper lip flaps with retaining the nasal columellar base incision has changed the traditional method to avoid the upper lip horizontal line scar, nasolabial angle contracture, while ensuring the columellar base blood supply is not damaged, with minimized and concealed scar. This surgical procedure is a safe and effective method and worth clinical application.

This experiment was to study the constituents of the roots of Viburnum setigerum through various column chromatographic techniques. Thirteen compounds were obtained and their structures were identified using chemical and spectroscopic methods as (7αH, 8'αH)-4, 4', 8α-trihydroxy-3, 3', 9-trimethoxy-7, 9'-epoxylignan (1), (7αH, 8'αH)-4, 4', 8α, 9-tetrahydroxy-3, 3'-dimethoxy-7, 9'-epoxylignan (2), alashinol G (3), alashinol F (4), (-)-secoisolariciresinol (5), (7R, 7'R, 8R, 8'S)-3, 3'-dimethoxy-7, 7'-epoxylignane -4, 4', 9, 9'-tetraol (6), (7αH, 8αH, 8'βH)-4, 4', 7'α, 9-tetrahydroxy-3, 3'-dimethoxy-7, 9'-epoxylignan (7), loganin (8), dihydroquercetin (9), protocatechuic acid (10), 4-hydroxy-3-methoxy-benzoic acid (11), adoxoside (12), and catechin (13). Compound 1 was a new compound. Compounds 3-7 and 11 were reported from the genus Viburnum for the first time. All compounds were separated from this plant for the first time.