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INTRODUCTION: [(68)Ga]Ga-P15-041 ([(68)Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry. METHODS: Subjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic. Dosimetry was performed with 6 whole body PET acquisitions and urine collection spanning 3 hours; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60-minute acquisition over a site of known or suspected disease followed by two whole body scans. Bootstrapping and subsampling of the acquired list-mode data were conducted to recommend image acquisition parameters for future clinical trials. RESULTS: Up to 233 MBq (6.3 mCi) of [(68)Ga]Ga-P15-041 was injected into 12 enrolled volunteers, 8 in dosimetry and 4 in dynamic cohorts. Radiotracer accumulated in known bone lesions and cleared rapidly from blood and soft tissue. The highest individual organ dose was 0.135 mSv/MBq in the urinary bladder wall. The average effective dose was 0.0173 ± 0.0036 mSv/MBq. An average injected activity of 166.5 MBq (4.5 mCi) resulted in absorbed dose estimates of 22.5 mSv to the urinary bladder wall, 8.2 mSv to the kidneys, and an effective dose of 2.9 mSv. Lesion signal to noise ratios on images generated from subsampled data were significantly higher for injected activities above 74 MBq (2 mCi) and were also significantly higher for imaging at 90 minutes than at 180 minutes post-injection. CONCLUSIONS: Dosimetry estimates are acceptable and [(68)Ga]Ga-P15-041 uptake characteristics in patients with confirmed bone metastases support its continued development. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Use of [(68)Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.

BackgroundThe main feature of natural orifice specimen extraction (NOSE) is its avoidance of an auxiliary abdominal incision. The safety of NOSE remains controversial. This study aimed to investigate the early safety of transanal NOSE in the treatment of sigmoid colon and upper rectal cancer from the follow aspects: clinical and pathological characteristics, inflammatory and immune indicators and postoperative complications.MethodsData from 125 patients diagnosed with sigmoid colon, and upper rectal cancer by gastrointestinal surgery in the First Affiliated Hospital of Wannan Medical College from January 2017 to June 2020 were analyzed. Patients were assigned to two surgical groups: Conventional laparoscopic-assisted radical resection for CRC (CLA, 75cases) and laparoscopic-assisted radical resection for CRC with NOSE (La-NOSE, 50 cases). The following were compared: clinical and pathological characteristics; intraoperative, bacteriological, and oncological results; postoperative inflammation and immune response indexes. Bacteriological results were obtained by aerobic and anaerobic bacterial culture of peritoneal wash fluid and oncology results by cytological analysis of peritoneal wash liquid exudation. Inflammation indicators included postoperative C-reactive protein (CRP) and procalcitonin (PCT) trend reactions. The immune index was the level of postoperative T lymphocytes (CD3, CD4/CD8). All data were analyzed by using SPSS statistical version 18.0 for windows. Measurement data are presented as the means ± standard deviations, and two-group comparisons were performed using the t-test. Comparisons of count data were performed using the chi-square test. p indicates that the difference was statistically significant.ResultsThe bacterial culture positive rate was not significant in the La-NOSE group (15/50 vs 19/75) than in the CLA group. The exfoliative cytology (EC) rate of the peritoneal wash fluid was 0 in both groups.The La-NOSE group had a significantly higher postoperative day 2(POD2) CRP and PCT level than the CLA group. The POD2 CD3 and CD4/CD8 levels were higher in the La-NOSE group than in the CLA group. There was no significant difference in the incidence of postoperative complications between the two groups (La-NOSE group vs CLA group: 3/50 vs 6/75) (p>0.05).ConclusionsAlthough the incidence of intra-abdominal contamination is high, it does not develop into a severe infectious disease, and does not lead to the implantation of free tumor cells into the abdominal cavity. Therefore, it is safe for the NOSE to treat colorectal cancer.

Summary: Background: In this study, we propose an improved Roux-en-Y (RY) surgical method by constructing a proximal jejunum pouch (PP-RY). Postoperative results were evaluated among patients with gastric cancer who underwent PP-RY and standard RY anastomosis. Methods: The clinical data of patients with gastric cancer who underwent laparoscopic total gastrectomy (LTG) in our center from May 2019 to May 2020 were collected retrospectively. We compared the short-term results of patients in the PP-RY and RY groups using 1:1 propensity score matching (PSM). Results: A total of 317 patients were selected, including those who received RY (n = 249) or PP-RY (n = 68) after LTG. After PSM, both groups had a sample size of 68. During the one-year follow-up period, the incidences of postoperative dumping syndrome (5.6%) and reflux esophagitis (14.8%) were significantly lower in the PP-RY group (P = 0.001 and P = 0.010, respectively). Weight loss (6.5 ± 2.0 kg) and albumin decrease (0.2 ± 0.1 g/dl) were significantly lower (P = 0.038 and P

A 26-year-old lactating mother presented with a 3-week history of abdominal pain, constipation and vomiting. She denied a history of alcohol abuse or other gastrointestinal problem. Contrast-enhanced CT revealed a small bowel obstruction caused by caecum cancer. Therefore, she underwent a right hemicolectomy and ileocolic anastomosis. Post-operatively, she gradually developed drowsiness, fainting and a rapid heart rate of 130. But blood tests were all normal. On the fourteenth postoperative day, she experienced two episodes of generalized tonic-clonic seizure. Neurologic examination revealed nystagmus, ophthalmoplegia and gait ataxia. She complained of impaired memory and blurred vision. Brain magnetic resonance image (MRI) showed bilaterally symmetric hyperintensities in paramedial thalami surrounding the third ventricle, dorsal brainstem and periaqueductal region in the axial T2-FLAIR images . Wernicke's encephalopathy (WE) was suspected and the patient was treated with Vitamin B1 immediately. Her symptoms improved rapidly, and a brain MRI two weeks later demonstrated marked resolution of the hyperintensities.

Estrogen receptor is an attractive target for the diagnosis and treatment of breast cancer. This article reports for the first time a dual-modality imaging agent targeting estrogen receptor that can use PET imaging to diagnose breast cancer and utilize fluorescence imaging to achieve intraoperative navigation. Fluorescence experiments show that [natGa] 1 has typical aggregate induced emission characteristics. Above the critical concentration, [natGa] 1 can form biocompatible nanomicelles. [natGa] 1 can quickly light up estrogen receptor positive MCF-7 cells. Cell uptake experiments show that [68Ga] 1 is mediated by estrogen receptor. Therefore, [nat/68Ga] 1 shows the characteristics of highly sensitive diagnosis and visualization of breast cancer, and can be used as a lead compound for the development of a novel PET-FI bimodal imaging agent targeting the estrogen receptor.

Background Tracheal extubation is commonly performed in the supine position. However, in patients undergoing abdominal surgery, the supine position increases abdominal wall tension, especially during coughing and deep breathing, which may aggravate pain and lead to abdominal wound dehiscence. The semi-Fowler’s position may reduce abdominal wall tension, but its safety and comfort in tracheal extubation have not been reported. We aimed to evaluate the safety and comfort of different extubation positions in patients undergoing abdominal surgery. Methods We enrolled 141 patients with an American Society of Anesthesiologists grade of I-III who underwent abdominal surgery. All patients were anesthetized with propofol, fentanyl, cisatracurium, and sevoflurane. After surgery, all patients were transferred to the post-anesthesia care unit (PACU). Patients were then randomly put into the semi-Fowler’s (n = 70) or supine (n = 71) position while 100% oxygen was administered. The endotracheal tube was removed after the patients opened their eyes and regained consciousness. Vital signs, coughing, and pain and comfort scores before and/or after extubation were recorded until the patients left the PACU. Results In comparison with the supine position, the semi-Fowler’s position significantly decreased the wound pain scores at all intervals after extubation (3.51 ± 2.50 vs. 4.58 ± 2.26, 2.23 ± 1.68 vs. 3.11 ± 2.00, 1.81 ± 1.32 vs. 2.59 ± 1.88, P = 0.009, 0.005 and 0.005, respectively), reduced severe coughing (8[11.43%] vs. 21[29.58%], P = 0.008) and bucking after extubation (3[4.29%] vs. 18[25.35%], P P = 0.007) and when leaving from post-anesthesia care unit (7.17 ± 2.27 vs. 6.44 ± 1.79, P = 0.034). The incidences of vomiting, emergence agitation, and respiratory complications were of no significant difference. Conclusion Tracheal extubation in the semi-Fowler’s position is associated with less coughing, sputum suction, and pain, and more comfort, without specific adverse effects when compared to the conventional supine position. Trial registration Chinese Clinical Trial Registry, ChiCTR1900025566. Registered on 1st September 2019.

Designing novel

Aromatase is an attractive target for the diagnosis and treatment of breast cancer. To combine the anti-photobleaching properties of Aggregation Induced Emission (AIE) with the high sensitivity and whole-body imaging characteristics of positron emission tomography (PET), we designed a bifunctional complexing agent with AIE characteristics by modifying the structure of tetraphenylethene, which is linked with triazole derivatives capable of complexing with natGa3+/68Ga3+ to obtain [natGa/68Ga] 2 for targeting the aromatase. [natGa] 2 has typical AIE characteristics, which can form uniform nanomicelles above the critical micelle concentration, and illuminate estrogen receptor (+) MCF-7 cells. [natGa] 2 itself is almost nonemissive in PBS buffer solution, but it turns on its fluorescence upon interaction with human aromatase, with a detection limit of 0.15 μg/mL [68Ga] 2 is easy to prepare and has high stability. Compared to the estrogen receptor that is negatively expressed by MDA-MB-231 cells, MCF-7 cells positively expressing estrogen have a higher uptake of [natGa] 2. The distribution of aromatase in a tumor can be co-localized by using [68Ga] 2. These results can be used to effectively assess estrogen receptor status and aromatase levels at the cellular level. We anticipate that this research could provide a new strategy for the fabrication of PET probes with AIE characteristics, providing useful probes for PET- FL (Fluorescence imaging) bimodal imaging.

We report the preparation of a novel glutamine derivative, (2S,4S)-2,5-diamino-4-(4-(2-fluoroethoxy)benzyl)-5-oxopentanoic acid, (2S, 4S)4-[

We report initial experience in synthesis of (2S,4R)-4-[

Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of estrogens. Imaging agents based on aromatase inhibitors (AIs) have been developed for a PET/SPECT study. A series of compounds was synthesized based on YM511, which has previously been used for breast cancer treatment. Two examples of these derivatives, 4-(((4-iodophenyl)methyl)-4H-1,2,4-triazol-4-yl-amino)-benzonitrile (5) and 4-((1H-imidazol-1-yl)(4-iodobenzyl)amino)benzonitrile (11), displayed potent binding affinities to human aromatase (IC50 = 0.17 and 0.04 nM, respectively). Biodistribution and autoradiographic studies revealed that [125I]5 and [125I]11 were highly accumulated in the stomach (16.21 and 10.88% dose/g, respectively) and ovaries (8.56 and 3.32% dose/g, respectively) of female rats. Log P of [125I]5 was 2.49, meaning good brain penetration. Autoradiograms of brain sections showed a high uptake in the bed nucleus of the stria terminalis and amygdala. These results suggest that [125I]5 and [125I]11 are potent p...

SummaryBackground Carbon dioxide (CO2) insufflation has been proposed as an alternative to air insufflation to distend the lumen in gastrointestinal (GI) endoscopy. Aim To perform a systematic review with meta-analysis of randomised controlled trials (RCTs) in which CO2 insufflation was compared with room air insufflation in GI endoscopy. Methods Electronic and manual searches were combined to search RCTs. After methodological quality assessment and data extraction, the efficacy and safety of CO2 insufflation were systematically assessed. Results Twenty-one RCTs [13 on colonoscopy, four on endoscopic retrograde cholangiopancreatography (ERCP), two on double-balloon enteroscopy (DBE), one on oesophagogastroduodenoscopy, and one on flexible sigmoidoscopy] were identified. For colonoscopy, CO2 insufflation resulted lower postprocedural pain intensity, and increased the proportion of patient without pain at 1 h (RR: 1.84, 95% CI: 1.37–2.47) and 6 h (RR: 1.28; 95% CI: 1.14–1.44) postprocedure. For ERCP, the pain-releasing effect of CO2 insufflation was not obvious (SMD: −1.48, 95% CI: −3.56, 0.59). CO2 insufflation revealed no consistent advantages in the RCTs of DBE, but was shown as safe as air insufflation in oesophagus/stomach endoscopic submucosal dissection in one study. pCO2 level showed no significant variation during these procedures. Conclusions Compared with air insufflation, CO2 insufflation during colonoscopy causes lower postprocedural pain and bowel distension without significant pCO2 variation. More RCTs are needed to assess its advantages in other GI endoscopic procedures.

Mitochondria dysfunction is associated with apoptotic resistance and metabolism of tumor cells. Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Certain gene mutations in mitochondria may lead to mitochondrial dysfunction. The p53 family plays a key role in the mitochondrial apoptosis pathway and acts as part of the molecular mechanisms underlying mitochondrial dysfunction in HCC. The novel genes found in the mitochondrial apoptosis signaling pathways, such as mfn2, play a role in the p53 network. In mitochondrial metabolism, expression of certain genes may be associated with apoptosis when they are involved in hepatocarcinogenesis. MicroRNAs have also been found to play a role in this process. Some genes may even exhibit multiple functions in the mitochondrial dysfunction of HCC. In HCC therapy, genes have also been found to influence the chemotherapeutic treatment by killing cells via the apoptosis pathway or autophagy. Investigation of mitochondrial dysfunction-related genes could potentially provide evidence for novel therapies that target HCC.

To explore the value of elastography score and strain rate ratio in the diagnosis of small breast malignant focus.We retrospectively analyzed 22 patients with breast small malignant foci less than 10 mm. Ultrasound characteristics were summed up in breast small cancer.On elastogram, 2 patients scored 3, 14 scored 4 and 6 scored 5.The average strain rate ratio of all foci was 4.76, and there was correlation between it and elastography scores.Ultrasonic elastography has important value in the diagnosis of breast small cancer.