TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.

Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.

"Clip coupled with an elastic ring" internal traction for endoscopic submucosal dissection of a rectal neuroendocrine tumor: a junior endoscopist experience.

A 64-year-old female was found a rectal neuroendocrine tumor (NET) for cancer screening examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic lesion (8.3*6.6 mm) originating from the submucosa layer. "Clip coupled with elastic ring" internal traction for endoscopic submucosal dissection (ESD) was used to remove the NET according to the procedure removal of a duodenal tumor1. The procedures are following: 1. Marking around the lesion with a margin of approximately 5 mm. 2. Submucosal injection and circumference incision around the lesion. 3. Applied clip coupled with elastic ring internal traction. 4. Submucosal injection. 5.Precise dissection was performed with the NET being en bloc resection. 5. Closed the mucosal defect. Finally, the Histopathology confirmed a neuroendocrine tumor.

One stone two birds - Submucosal tunneling endoscopic resection for a large esophageal submucosal mass and esophageal diverticulum.

A-35-year-old woman presented our hospital with half a year's history of solid food dysphagia. An upper gastrointestinal endoscopy revealed a large submucosal mass in an esophageal diverticulum near the gastroesophageal junction. Endoscopic ultrasound (EUS) confirmed a hypoechoic lesion arising from the muscularis propria layer with the size of 25*14 mm. Therefore, submucosal tunneling endoscopic resection (STER) was proposed to remove the large submucosal lesion in addition to targeted septotomy of the esophageal diverticula. A 2-cm longitudinal mucosal access was made at 3 cm above the submucosal lesion, and a submucosal longitudinal tunnel was created until the submucosal lesion revealed using a DualKnife (Olympus, Japan). Meticulous resection was performed with the DualKnife, and the lateral border of the lesion was dissected from muscularis propria layer. It was completely removed the lesion with en bolc resection, and dissected the septum of the diverticulum using the DualKnife. The tunnel access was closed with several hemoclips. Finally, it has been demonstrated to achieve a perfect outcome for the patient. The patient was discharged three days later with symptom resolved on follow-up and to date.

A novel three traction rings device with endoscopic submucosal dissection (ESD) in the removal of a large superficial duodenal adenoma.

Endoscopic treatment is generally recommended for the duodenal epithelial adenoma. Although underwater endoscopic mucosal resection (UEMR) has become established as an effective modality for the superficial duodenal adenoma. However, it is difficult to completely remove a large superficial duodenal adenoma with en bloc resection. Endoscopic submucosal dissection (ESD) is commonly performed to remove a large superficial duodenal adenoma, whereas which is technically challenged with severe adverse events. It has reported that entire traction using clip-and-nylon ring with ESD was effective and safe in the removal of a large rectal sessile serrated adenoma (SSA). Herein, we shared our experience of the novel three traction rings device in the treatment of a large superficial duodenal adenoma.

New options for endoscopic treatment of gastric varices.

BACKGROUND: Gastric venous bleeding is one of the most common adverse events in liver cirrhosis. The therapeutic effect of isolated gastric varices is relatively clear. However, there is no appropriate clinical and endoscopic treatment for extensive variceal bleeding in the gastric fundus and body. METHODS: In this patient with non-isolated gastric varices, we decided to perform endoscopic multi-point ligation of the obvious varices in the gastric fundus and body. RESULTS: In this patient, endoscopic treatment of gastric varices with bleeding after surgery achieved a significant therapeutic effect. Reexamination of gastroscopy at 3 months after operation showed that multiple scars were formed in the gastric fundus and fundus, and no obvious varices were found. CONCLUSIONS: For patients with non-isolated gastric varices, endoscopic multi-point ligation is a safe and effective treatment option for the varices with obvious gastric fundus and body.

An unpredictable gastrointestinal bleed.

A 65-year-old male complained of persistent melena for 6 days, and displayed anemia symptoms without hematemesis, vomiting, and abdominal distention. He was diagnosed as ruptured aneurysm of aortic sinus Valsalva, and had received coronary artery occlusion 1 month ago. After the operation, he was continually prescribed clopidogrel 75 mg once daily. The laboratory examination showed blood hemoglobin concentration was 60 g/L without other conspicuous abnormality. Unfortunately, neither esophagogastroduodenoscopy (EGD) nor colonoscopy found no obvious bleeding lesions. And abdominal computed tomography angiography (CTA) and enhanced computed tomography (CT) showed no obvious abnormal findings. Moreover, capsule endoscopy revealed small intestinal with mucosal erosion (Figure 1A). After discontinued clopidogrel, blood transfusion, and support therapy, his symptoms was resolved with negative fecal occult blood, continued clopidogrel 75 mg once daily, and uneventfully discharged 1 week later.

Diagnostic significance of EyeMAX in diagnosing patients with tumor in the terminal end of the common bile duct.

A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver. There are many etiologies of biliary stricture, the most common and ominous of which is malignancy, either primary or metastatic.It is difficult to obtain pathological tissue of the terminal end of the common bile duct. A 72-year-old woman, complained of abdominal pain for 2 months, underwent cholecystectomy for acute cholecystitis 11 years ago. Abdominal CT and MRI examination revealed soft tissue occupation (12*8 mm) in the duodenal papillary area, and endoscopic ultrasonography revealed a hypoechoic lesion (11.1*10.7 mm) in the ampulla. We performed ERCP, and intraoperative biliary cell brushing on the patient, but no positive pathological results were obtained. We further performed novel 9F digital single operator cholangioscopy system (DSOC) (eyeMAX, Micro-Tech, Nanjing, China) and observed intraoperative hyperemia and edema of the mucosa in the terminal end of the common bile duct, presenting fish-like changes with mucous attachment and clear lesion boundaries. The pathological results suggested cholangiocarcinoma.

A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Mutations in the Pectin Methyltransferase QUASIMODO2 Influence Cellulose Biosynthesis and Wall Integrity in Arabidopsis.

Pectins are abundant in the cell walls of dicotyledonous plants, but how they interact with other wall polymers and influence wall integrity and cell growth has remained mysterious. Here, we verified that QUASIMODO2 (QUA2) is a pectin methyltransferase and determined that QUA2 is required for normal pectin biosynthesis. To gain further insight into how pectin affects wall assembly and integrity maintenance, we investigated cellulose biosynthesis, cellulose organization, cortical microtubules, and wall integrity signaling in two mutant alleles of Arabidopsis (Arabidopsis thaliana) QUA2, qua2 and tsd2 In both mutants, crystalline cellulose content is reduced, cellulose synthase particles move more slowly, and cellulose organization is aberrant. NMR analysis shows higher mobility of cellulose and matrix polysaccharides in the mutants. Microtubules in mutant hypocotyls have aberrant organization and depolymerize more readily upon treatment with oryzalin or external force. The expression of genes related to wall integrity, wall biosynthesis, and microtubule stability is dysregulated in both mutants. These data provide insights into how homogalacturonan is methylesterified upon its synthesis, the mechanisms by which pectin functionally interacts with cellulose, and how these interactions are translated into intracellular regulation to maintain the structural integrity of the cell wall during plant growth and development.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Endoscopic submucosal dissection coupled with "modified clip coupled with elastic ring" traction removing rectal neuroendocrine tumor.

A 50-year-old female complained of discomfort of lower abdomen, and a colonoscopy revealed a rectal neuroendocrine tumor (NET). Endoscopic ultrasonography (EUS) showed a hypoechoic lesion (8.5*7.6 mm) originating from the submucosa layer. Endoscopic submucosal dissection (ESD) coupled with "modified clip coupled with elastic ring" traction was performed to remove the NET. Following procedures previously described, we made a subtle change.

Ligation-assisted endoscopic resection to remove a small esophageal lesion (< 20 mm) originating from muscularis propria.

A 35-year-old female complained of slight dysphagia for 3 months. Her physical examination and laboratory tests were unremarkable. Esophagogastroduodenoscopy (EGD) revealed a submucosal tumor (SMT) in the lower esophagus. Then, endoscopic ultrasonography (EUS) revealed that a hypoechoic echo lesion (10mm*12mm) originated from muscularis propria. Subsequently, ligation-assisted endoscopic resection was performed to remove the esophageal lesion. The steps were briefly described as follows: Marking dots in the SMT, and injecting submucosally beneath the marking dots. Incising apical mucosal surface around the marking dots Assembling an endoloop and ligation device (MAJ-339; Olympus). Ligating the SMT with endoloop. Cold snare the SMT.Ligating the defect using another endoloop. Histopathology confirmed a leiomyoma). After 2 months follow-up, EGD revealed healing of the esophageal lesion.

An unexpected gastric cardia submucosal lesion.

An esophagogastroduodenoscopy revealed a submucosal lesion in the gastric cardia of a 55-year-old man.Endoscopic ultrasonography showed a hypoechoic echo lesion originated from the muscularis propria layer considering a leiomyoma or stromal tumor.a submucosal tunneling endoscopic resection was successfully performed to remove the lesion and the diagnosis is hepatoid adenocarcinoma.This is the first report on a case of gastric HAC originated from submucous layer.

A submucosal lesion of the rectum: an unexpected MALT.

A 57-year-old female was found a 12 mm × 10 mm submucosal lesion in the rectum with a smooth mucosa and telangiectasia The lesion was considered as a neuroendocrine tumor, and removed by endoscopic submucosal dissection (ESD) It was finally diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma with negative margin by pathological examination and histopathological test. MALT lymphoma in the rectum is rare and difficult to diagnose without histopathological test. In this case, the characteristic of this case is telangiectasia on the surface of lesion. Therefore, our findings suggested small lesion in rectum but big in impact.

miR-183/TMSB4Y, a new potential signaling axis, involving in the progression of laryngeal cancer via modulating cell adhesion.

Laryngeal cancer (LCa) is a prevalent malignant head and neck cancer with relatively unclear pathogenesis. A prior study has suggested that miR-183 differentially expressed in laryngeal-related malignancies, but its accurate role has not been fully ascertained in LCa. miR-183 expression in LCa tissues and cells was detected assisted by TCGA/GEO databases or qRT-PCR assay, relatively. Target genes of miR-183 were predicted via accessing to TargetScan website. Luciferase activity analysis was conducted to determine the relationship between miR-183 and its possible target. CCK-8, colony formation and transwell invasion and migration experiments were implemented to measure LCa cell viability, invasion and migration. Western blot assay was utilized to evaluate cell adhesion and EMT-related proteins expressions. The expression of miR-183 was expressed in LCa tissue samples and cells at higher levels than normal controls. Upregulation of miR-183 facilitated Hep-2 and TU212 cells viability, while miR-183 reduction inhibited the proliferative potential of Hep-2 and TU212 cells. TMSB4Y was determined as a possible target of miR-183, and its expression was decreased in LCa. LCa patients with low TMSB4Y expression had poorer outcomes relative to that with high TMSB4Y expression. TMSB4Y overturned the promoting impacts of miR-183 on the LCa cellular malignant behaviors, including cell proliferation, colonogenicity, invasion and migration. miR-183 overexpression inhibited cell adhesion through inhibiting TMSB4Y expression. Overall, all results elucidated that miR-183, as an oncogenic molecule in LCa, may be used to predict the prognosis of LCa patients by targeting TMSB4Y.

The feasibility and safety of disposable endoscope vs. conventional endoscope for upper gastrointestinal tract examination: a multicenter, randomized, parallel, non-inferiority trial.

BACKGROUND: A disposable upper gastrointestinal endoscope can effectively decrease infectious outbreaks associated with endoscope reuse. In the present study, we aimed to evaluate the feasibility and safety of a disposable endoscope for upper gastrointestinal examination. METHODS: In a prospective, randomized trial, 144 upper endoscopic procedures were allocated to either the disposable endoscope group or the conventional endoscope group. The primary outcomes were rates of excellent and good image qualities and maneuverability satisfaction. The second outcome included procedure duration, endoscopic diagnosis, and adverse events. RESULTS: A total of 144 subjects were enrolled in the present analysis and prospectively randomized to 2 study groups. Finally, 70 and 69 subjects were enrolled in the novel disposable endoscope group and the conventional endoscope group, respectively, due to the schedule cancellation of 5 subjects. The baseline characteristics of the patients were similar in both groups. The excellent and good image quality rates and maneuverability satisfaction of the novel disposable endoscope were not inferior to the conventional endoscope (p = 0.99 and p = 0.99, respectively). Moreover, no significant between-group difference was observed in the endoscopic results and adverse events (p = 0.30 and p = 1, respectively). However, the procedure duration in the novel disposable endoscope was longer compared with the conventional endoscope (8.40 ± 4.28 min vs. 5.12 ± 2.65 min, p < 0.001). CONCLUSIONS: The novel disposable endoscope was as safe, effective, and maneuverable as a conventional endoscope. However, the novel disposable endoscope was associated with a longer procedure duration.

Endoscopic resection in combination with ligation for the treatment of duodenal subepithelial lesions: a single-center experience.

INTRODUCTION AND AIM: duodenal subepithelial lesions (SELs) are increasingly detected during endoscopic examinations. However, no feasible and safe methods are available to remove duodenal SELs. The present study aimed to assess the feasibility and safety of endoscopic resection in combination with ligation (ER-L) for the removal of duodenal SELs. PATIENTS AND METHODS: a total of 101 patients with duodenal SELs underwent ER-L from February 2010 to February 2020. The primary outcomes were complete resection, en bloc resection and R0 resection. The secondary outcomes included procedure duration, bleeding, perforation and residual lesions. A total of 101 patients with 101 duodenal SELs (ranged from 8.4 mm to 20.2 mm in size) were included in the study. RESULTS: most of the SELs (95.1 %) originated from the submucosal layer and were successfully removed using ER-L. The rates of complete resection, en bloc resection and R0 resection were 100 %, 96.0 % and 88.1 %, respectively. The median procedure duration was eight minutes. There were no severe complications, except for four patients who developed post-procedure bleeding (4.0 %) and recovered after conservative treatment. Furthermore, no residual lesions were detected during the follow-up period (median of 36 months). In fact, logistic regression analysis showed that the size of duodenal SELs was an independent factor for R0 resection during the ER-L procedure. CONCLUSION: in conclusion, ER-L is feasible and safe to remove duodenal SELs that originate from the submucosal layer and are less than 20 mm. However, the feasibility and safety of the ER-L should be further confirmed when removing the duodenal SELs that originate from the muscularis propria (MP) layer and are larger than 20 mm in diameter.

Predicting Division Planes of Three-Dimensional Cells by Soap-Film Minimization.

One key aspect of cell division in multicellular organisms is the orientation of the division plane. Proper division plane establishment contributes to normal plant body organization. To determine the importance of cell geometry in division plane orientation, we designed a three-dimensional probabilistic mathematical model to directly test the century-old hypothesis that cell divisions mimic soap-film minima. According to this hypothesis, daughter cells have equal volume and the division plane occurs where the surface area is at a minimum. We compared predicted division planes to a plant microtubule array that marks the division site, the preprophase band (PPB). PPB location typically matched one of the predicted divisions. Predicted divisions offset from the PPB occurred when a neighboring cell wall or PPB was directly adjacent to the predicted division site to avoid creating a potentially structurally unfavorable four-way junction. By comparing divisions of differently shaped plant cells (maize [Zea mays] epidermal cells and developing ligule cells and Arabidopsis thaliana guard cells) and animal cells (Caenorhabditis elegans embryonic cells) to divisions simulated in silico, we demonstrate the generality of this model to accurately predict in vivo division. This powerful model can be used to separate the contribution of geometry from mechanical stresses or developmental regulation in predicting division plane orientation.

A wall with integrity: surveillance and maintenance of the plant cell wall under stress.

The structural and functional integrity of the cell wall needs to be constantly monitored and fine-tuned to allow for growth while preventing mechanical failure. Many studies have advanced our understanding of the pathways that contribute to cell wall biosynthesis and how these pathways are regulated by external and internal cues. Recent evidence also supports a model in which certain aspects of the wall itself may act as growth-regulating signals. Molecular components of the signaling pathways that sense and maintain cell wall integrity have begun to be revealed, including signals arising in the wall, sensors that detect changes at the cell surface, and downstream signal transduction modules. Abiotic and biotic stress conditions provide new contexts for the study of cell wall integrity, but the nature and consequences of wall disruptions due to various stressors require further investigation. A deeper understanding of cell wall signaling will provide insights into the growth regulatory mechanisms that allow plants to survive in changing environments.