Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

With the increasing maturity of laparoscopic surgery, laparoscopic radical resec-tion of colorectal cancer has been widely used in colorectal surgery. Accurate localization of colorectal tumors and surgical margins in the absence of tactile sensation during surgery, ensuring sufficient blood flow perfusion at the anastomotic site and effectively reducing the incidence of anastomotic leakage have become barriers to the development of laparoscopic radical resection of colorectal cancer. The application of indocyanine green fluorescence imaging (ICG-FI) technology is expected to provide feasible solutions to the above-mentioned problems. Through this technology, accurate localization of colorectal tumors, evaluation of blood supply to the anastomotic site, lymphatic system imaging, detection of colorectal liver metastases, and protection of pelvic autonomous nerves and ureters can be achieved during laparoscopic surgery, thereby further improving the surgical quality of laparoscopic radical resection of colorectal cancer. However, the clinical application of ICG-FI technology in colorectal surgery is relatively short, which is still in the stage of exploration and experience accumulation, and there are few guideline or consensus available for reference. Therefore, the authors aim to provide a reference for the clinical application of this technology by reviewing and summarizing relevant literature based on different application types of ICG in colo-rectal cancer surgery.

Objective: To investigate the impact of COVID-19 on treatment of patients with acute ST segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods: This was a multicenter retrospective study. STEMI patients undergoing PPCI from January 1, 2019 to December 31, 2021 were selected, based on the data of Xinnaolvsetongdao App. Clinical data and treatment time indicators, including symptom to first medical contact (S-FMC), symptom to door (StoD), first medical contact to ECG (FMC-ECG), first medical contact to guide wire (FMC-W), door to balloon (DtoB) and total ischemic time in 2019, 2020 and 2021 were compared. STEMI patients aged<60 years were sub-grouped as the young and middle-aged group, and STEMI patients aged≥60 years were sub-grouped as the elderly group. Results: A total of 7 435 (3 305 in 2019, 1 796 in 2020 and 2 334 in 2021) STEMI patients aged (59.6±12.6) years undergoing PPCI were included in this analysis. There were 5 990 males. For STEMI patients with PPCI in 2019, 2020 and 2021, FMC-ECG was 3 (1, 5) min, 3(1, 7) min and 4 (1, 7) min. FMC-W was 73 (56, 87) min, 78 (62, 95) min and 77 (62, 87) min. DtoB was 73 (56, 85) min, 78 (62, 95) min and 77 (62, 86) min. Total ischemic time was 189 (130, 273) min, 196 (138, 295) min and 209 (143, 276) min. FMC-ECG, FMC-W, DtoB and total ischemic time were longer in 2020 and 2021 than in 2019 (all P<0.05). The proportions of patients with FMC-ECG≤10 min (88.4% (1 588/1 796) vs. 92.7% (3 064/3 305), P<0.05), FMC-W≤120 min (87.9% (1 579/1796) vs. 91.7% (3 030/3 305), P<0.05) and DtoB≤90 min (72.3% (1 298/1 796) vs. 80.8% (2 672/3 305), P<0.05) were lower in 2020 than in 2019, whereas no differences were observed in the proportions of patients with FMC-ECG≤10 min (91.3% (2 131/2 334) vs. 92.7% (3 064/3 305), P=0.054), FMC-W≤120 min (92.0% (2 148/2 334) vs. 91.7% (3 030/3 305), P=0.635) and DtoB≤90 min (80.0% (1 867/2 334) vs. 80.8% (2 672/3 305), P=0.424) in 2021 compared with 2019. In the subgroup analysis, the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2019 (all P<0.05). The proportions of patients with FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2021(all P<0.05). No differences were observed in the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min between the two group in 2020 (all P>0.05). Conclusions: Affected by the COVID-19, there is a reduction in the number of PPCI cases and treatment delays in STEMI patients, especially in the elderly. After adjusting the treatment strategy and widely applying the Xinnaolvsetongdao APP, the above indicators are significantly improved in 2021 as compared with 2020.
Aged ; Male ; Middle Aged ; Humans ; ST Elevation Myocardial Infarction ; Beijing ; COVID-19 ; Retrospective Studies ; Anterior Wall Myocardial Infarction ; Arrhythmias, Cardiac ; Percutaneous Coronary Intervention

Objective: To investigate the impact of COVID-19 on treatment of patients with acute ST segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods: This was a multicenter retrospective study. STEMI patients undergoing PPCI from January 1, 2019 to December 31, 2021 were selected, based on the data of Xinnaolvsetongdao App. Clinical data and treatment time indicators, including symptom to first medical contact (S-FMC), symptom to door (StoD), first medical contact to ECG (FMC-ECG), first medical contact to guide wire (FMC-W), door to balloon (DtoB) and total ischemic time in 2019, 2020 and 2021 were compared. STEMI patients aged<60 years were sub-grouped as the young and middle-aged group, and STEMI patients aged≥60 years were sub-grouped as the elderly group. Results: A total of 7 435 (3 305 in 2019, 1 796 in 2020 and 2 334 in 2021) STEMI patients aged (59.6±12.6) years undergoing PPCI were included in this analysis. There were 5 990 males. For STEMI patients with PPCI in 2019, 2020 and 2021, FMC-ECG was 3 (1, 5) min, 3(1, 7) min and 4 (1, 7) min. FMC-W was 73 (56, 87) min, 78 (62, 95) min and 77 (62, 87) min. DtoB was 73 (56, 85) min, 78 (62, 95) min and 77 (62, 86) min. Total ischemic time was 189 (130, 273) min, 196 (138, 295) min and 209 (143, 276) min. FMC-ECG, FMC-W, DtoB and total ischemic time were longer in 2020 and 2021 than in 2019 (all P<0.05). The proportions of patients with FMC-ECG≤10 min (88.4% (1 588/1 796) vs. 92.7% (3 064/3 305), P<0.05), FMC-W≤120 min (87.9% (1 579/1796) vs. 91.7% (3 030/3 305), P<0.05) and DtoB≤90 min (72.3% (1 298/1 796) vs. 80.8% (2 672/3 305), P<0.05) were lower in 2020 than in 2019, whereas no differences were observed in the proportions of patients with FMC-ECG≤10 min (91.3% (2 131/2 334) vs. 92.7% (3 064/3 305), P=0.054), FMC-W≤120 min (92.0% (2 148/2 334) vs. 91.7% (3 030/3 305), P=0.635) and DtoB≤90 min (80.0% (1 867/2 334) vs. 80.8% (2 672/3 305), P=0.424) in 2021 compared with 2019. In the subgroup analysis, the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2019 (all P<0.05). The proportions of patients with FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2021(all P<0.05). No differences were observed in the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min between the two group in 2020 (all P>0.05). Conclusions: Affected by the COVID-19, there is a reduction in the number of PPCI cases and treatment delays in STEMI patients, especially in the elderly. After adjusting the treatment strategy and widely applying the Xinnaolvsetongdao APP, the above indicators are significantly improved in 2021 as compared with 2020.
Aged ; Male ; Middle Aged ; Humans ; ST Elevation Myocardial Infarction ; Beijing ; COVID-19 ; Retrospective Studies ; Anterior Wall Myocardial Infarction ; Arrhythmias, Cardiac ; Percutaneous Coronary Intervention

Objective:To design a laparoscopic partial renal blood flow blocker (LPRB), and to explore the design rationality and effect of LPRB on blocking the blood flow of local renal tissue in rabbit kidney experiment.Methods:⑴ Design.According to the anatomical characteristics of the renal blood flow from the center to the periphery in the human, pig and rabbit, the blood flow at the distal part of the compression area could be blocked by the compression of the medial kidney tissue. LPRB included the first pressure arm, the second pressure arm and shaft. A built-in torsion spring made the two ends of the pressure arm to automatically close. The ends of pressure arm were provided with an arc-shaped compression component, on which, there were multiple adaptive compression plates. ⑵ Fabrication. 3D printer printed the finished product with titanium alloy material. ⑶ Animal experiments. Five New Zealand rabbits were anesthetized and fixed on the operating table in a semi-lateral position, with a lateral abdominal incision. Kidneys were exposed, only the renal pedicle vessels were retained. According to different methods of blocking blood flow, they were divided into conventional group and LPRB group for self-control. The effect of blocking blood flow was observed. The clamping force of LPRB was detected, and the degree of tissue damage at the clamping site was observed by naked eye and pathology.Results:LPRB had been licensed as a utility model and apperance patent. The device was successfully made from titanium alloy by 3D printer. In the experiment, the device was easily placed and removed. The two pressure arms were automatically closed and fixed under the action of torsion spring. The angle of the compression arm could be adjusted according to the position of clamping. The self-adaptive compression plates might be inclined in order to be consistent with the shape of the kidney; The pressure of LPRB was sufficient and the hemostasis was complete.Conclusions:LPRB is basicly rational and safe, and it can realize the partial hemostasis of the excised part and guarantee the blood flow of other parts at the same time. However, the larger size and harder adaptive component need to be improved in the future.

Objective To investigate the therapeutic effect of Radish Seed Chengqi Decoction combined with glutamine for treatment of patients with sepsis complicated with paralytic ileus. Methods Sixty patients with septic ileus admitted to the Department of Emergency Intensive Care Unit (EICU) of Tianjin Medical University General Hospital from August 2017 to January 2019 were enrolled. The Western medicine treatment group (30 cases) received routine Western medical methods including intravenous drip of glutamine, etc. for symptomatic treatment, and the Radish Seed Chengqi Decoction group (30 cases), based on the treatment in the Western medicine group, were additionally given the decoction by nasal feeding and retention enema twice a day, once 100 mL with the course of 7 days in both groups. The herbal prescription of Radish Seed Chengqi Decoction contained rhubarb 24 g (decocted later), sodium sulfate 15 g (mixed with water to take), magnoliae cortex 15 g, orange frui 10 g, aucklandiae 10 g, henan achyranthes root 10 g and radish seed 15 g, constituting one dose, two doses one day given to a patient, making one dose of herbal medicine to 200 mL of decoction for nasal feeding and retention enema, once 100 mL respectively, twice a day for 7 days. After treatment, the changes of survival rate in ICU, the total effective rate and the level of procalcitonin (PCT) were observed in both groups. Results After treatment, the total effective rate in Radish Seed Chengqi Decoction group was significantly higher than that in the Western medicine treatment group [83.33% (25/30) vs. 66.67% (20/30), P < 0.05], and the ICU 7-day survival rate in Radish Seed Chengqi Decoction group was also significantly higher than that in Western medicine treatment group [90.00% (27/30) vs. 76.67% (23/30), P < 0.05]. After treatment, the levels of PCT (μg/L) in both groups were significantly decreased compared with those before the treatment (Western medicine treatment group: 3.38±1.72 vs. 6.43±3.29, and Radish Seed Chengqi Decoction group: 2.39±1.24 vs. 6.78±2.31, both P < 0.05), and the degree of decrease of PCT in radish seed chengqi decoction group was more obvious than that in Western medicine treatment group (μg/L: 2.39±1.24 vs. 3.38±1.72, P < 0.05). Conclusion Applying alanyl glutamine combined with Radish Seed Chengqi Decoction for treatment of patients with sepsis complicated with paralytic ileus can significantly improve the clinical symptoms, reduce the PCT level and elevate the survival rate of patients.

Objective To explore the three dimensional time of flight (3D-TOF) MR angiography (MRA) manifestations and its clinical significance in duplicated middle cerebral artery (DMCA). Methods The clinical and MRA data of 37 patients with DMCA, admitted to our hospital from July 2013 to April 2017, were collected. The original images were reconstructed by maximum immensity projection (MIP). The imaging features of origin, sizes, walking and distribution of DMCA were observed, and DMCA classification was performed. Results Among the 37 patients with DMCA, 24 patients with type A were from the internal carotid artery (ICA) terminal, and the proximal part was parallel to the MCA-M1 segment; 13 patients with type B were originated between the anterior choroidal artery and the ICA terminal, the proximal end in 8 patients was parallel to the M1 section of the middle cerebral artery and the proximal end in 5 patients was obviously curved to the temporal lobe. The relative size of type A was 0.94±0.07 (0.72-1.00), while that of type B was 0.68±0.22 (0.31-1.00), with statistically significant difference (P<0.05). Conclusions The 3D-TOF-MRA can display the detailed information of DMCA, which can be used as the important methods for its diagnosis. And this vascular variation has important clinical significance, and awareness on this vascular variation should be strengthened in clinical work.

Objective To probe the precision of the magnetic resonance spectroscopy (MRS)in assessing the fat content in the vertebral bone marrow and the changes at different vertebrae.Methods A total of 46 female volunteers were recruited in this study. After routine MRI examination,single voxel (SV)was chosen for the 1 H-MRS acquisition at L1 -L4 vertebral body.Thirty subjects were scanned twice to evaluate the precision of MRS.The fat fraction (FF%),unsaturation index (UI)and coefficients of variation (CV) were calculated by amplitude and area under the peak respectively.The changes of fat content in marrow at L1 -L4 vertebrae was further evaluated.Results The CV related to peak amplitude was 1.7% in quantification of vertebral FF%,while the CV related to peak area was 6.3%.In quantification of vertebral UI,the CV related to amplitude and area was 2.4% and 7.8% respectively.The FF% was ascended from L1 to L4,while UI of bone marrow declined.A significant correlation was observed between FF% and UI (r=-0.714,P <0.01).The correlation of FF% among L1 -L4 were also significantly observed (r =0.612 -0.923,P <0.01). Conclusion MRS at 3.0 T provides reliable measurement for marrow fat content with a good precision associated with amplitude. Meanwhile,there is a preferential increase in saturated lipids compared to unsaturated lipids from L1 to L4.There is a high correlation of FF%among L1-L4.MRS is a valuable tool for providing complementary information on osteoporosis research.

OBJECTIVETo explore the efficacy of different procedures for refractory constipation complicated with megacolon.

METHODSClinical data of 112 patients of refractory constipation complicated with megacolon undergoing surgery in our institute from June 2007 to January 2013 were retrospectively analyzed. Of these 112 patients, the duration of constipation ranged from 4 to 22 years. Seventy-four patients had previous abdominal operations. Surgical procedures: (1)Jinling procedure (subtotal colectomy plus ascending colorectal posterior wall side-to-side anastomosis, n=81), including 24 laparoscopy-assisted procedures, 18 terminal ileostomies. (2)total colectomy plus ileorectal side-to-side anastomosis(n=18). (3)total colectomy plus end ileostomy, and ileorectal posterior wall side-to-side anastomosis 6 months later(n=13). The end ileostomy was reversed 6 months after operation.

RESULTSThe successful rate was 100%, and no surgery-related deaths were found. Postoperative complications included early diarrhea (90 cases, 80.4%), anal pain and incomplete evacuation (22 cases, 19.6%), urinary retention within 24-48 h after catheter removal (16 cases, 14.2%), anastomosis bleeding (9 cases, 8.0%), anastomosis leakage (6 cases, 5.4%), and intestinal obstruction (15 cases, 13.4%). Six patients with intestinal obstruction underwent adhesiolysis, and others were managed by conservative therapy. At the postoperative follow-up at 6 months, the Wexner constipation score was significantly reduced (5.8-8.3 vs. 21.4-28.7, P<0.01), and malnutrition improved as well.

CONCLUSIONSurgical intervention results in good efficacy for refractory constipation complicated with megacolon.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anastomosis, Surgical ; methods ; Colectomy ; methods ; Constipation ; complications ; surgery ; Female ; Humans ; Ileostomy ; Male ; Megacolon ; complications ; surgery ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUND:Parathyroid hormone related peptides are accompanied by the syndrome of humoral hypercalcemia of malignancy. As a potential therapeutic drug of promoting the healing of bone fracture, parathyroid hormone related peptides have significant clinical application value.
OBJECTIVE:To explore the regulating effects of parathyroid hormone related peptides in diabetic osteoporotic fracture
METHODS:A computer-based online research of CNKI and PubMed databases was performed to col ect articles published between 1990 and 2013, with the key words“parathyroid hormone related peptides, diabetes, osteoporotic fracture”in Chinese and English. There were 1 279 articles after the initial survey. A total of 43 articles were included according inclusion and exclusion criteria.
RESULTS AND CONCLUSION:Animal and clinical experiments demonstrated that parathyroid hormone related peptides notably accelerate bone fracture healing, and improve the repair process of islet cellfunction defects that are related with diabetes. Meanwhile, as an analogue, parathyroid hormone has been identified as clinical medication in the treatment of fracture. But the appropriate dose, and method of application at the different stages of bone fracture healing and the problem of drug combination need further investigation.