Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Standardize the surgical technique and clarify the oncologic significance of robotic D3-D4 lymphadenectomy for upper rectum and sigmoid colon cancer with clinically more than N2 lymph node metastasis.

BACKGROUND: The territory of D3-D4 lymphadenectomy for upper rectal and sigmoid colon cancer varies, and its oncological efficacy is unclear. This prospective study aimed to standardize the surgical technique of robotic D3-D4 lymphadenectomy and clarify its oncologic significance. METHODS: Patients with upper rectal or sigmoid colon cancer with clinically suspected more than N2 lymph node metastasis were prospectively recruited to undergo standardized robotic D3-D4 lymphadenectomy. Immediately postsurgery, the retrieved lymph nodes were mapped to five N3-N4 nodal stations: the inferior mesenteric artery, para-aorta, inferior vena cava, infra-renal vein, and common iliac vessels. Patients were stratified according to their nodal metastasis status to compare their clinicopathological data and overall survival. Univariate and multivariate analyses were performed to determine the relative prognostic significance of the five specific nodal stations. Surgical outcomes and functional recovery of the patients were assessed using the appropriate variables. RESULTS: A total of 104 patients who successfully completed the treatment protocol were assessed. The standardized D3-D4 lymph node dissection harvested sufficient lymph nodes (34.4±7.2) for a precise pathologic staging. Based on histopathological analysis, 28 patients were included in the N3-N4 nodal metastasis-negative group and 33, 34, and nine patients in the single-station, double-station, and triple-station nodal metastasis-positive groups, respectively. Survival analysis indicated no significant difference between the single-station nodal metastasis-positive and N3-N4 nodal metastasis-negative groups in the estimated 5-year survival rate [53.6% (95% CI: 0.3353-0.7000) vs. 71.18% (95% CI: 0.4863-0.8518), P=0.563], whereas patients with double-station or triple-station nodal metastatic disease had poor 5-year survival rates (24.76 and 22.22%), which were comparable to those of AJCC/UICC stage IV disease than those with single-station metastasis-positive disease. Univariate analysis showed that the metastatic status of the five nodal stations was comparable in predicting the overall survival; in contrast, multivariate analysis indicated that common iliac vessels and infra-renal vein were the only two statistically significant predictors (P<0.05) for overall survival. CONCLUSIONS: Using a robotic approach, D3-D4 lymph node dissection could be safely performed in a standardized manner to remove the relevant N3-N4 lymphatic basin en bloc, thereby providing significant survival benefits and precise pathological staging for patients. This study encourages further international prospective clinical trials to provide more solid evidence that would facilitate the optimization of surgery and revision of the current treatment guidelines for such a clinical conundrum.

Changing patterns and surgical outcomes of small bowel obstruction in the era of minimally invasive surgery for colorectal cancer.

INTRODUCTION: This study aimed to investigate whether the incidence, patterns, and surgical outcomes of small bowel obstruction (SBO) have changed in the era of minimally invasive surgery (MIS) for primary colorectal cancer (CRC). METHODS: Consecutive patients who underwent laparotomy for SBO were divided into MIS and traditional open surgery (TOS) groups based on the previous colorectal cancer operation technique used. The MIS group was selected from 1544 consecutive patients who underwent MIS as a treatment for primary CRCs between 2014 and 2022, while the TOS group was selected from 1604 consecutive patients who underwent TOS as a treatment for primary CRCs between 2004 and 2013. The demographics, clinicopathological features, and surgical outcomes were compared between the two groups. RESULTS: The SBO incidence in patients who underwent MIS for primary CRC was significantly lower than that in patients who underwent TOS (4.4%, n =68/1544 vs. 9.7%, n =156/1604, P <0.0001). Compared with the TOS group, the MIS group had significantly different ( P <0.0001) SBO patterns: adhesion (48.5 vs. 91.7%), internal herniation (23.5 vs. 2.6%), external herniation (11.8 vs. 1.9%), twisted bowel limbs (4.4 vs. 0.6%), ileal volvulus with pelvic floor adhesion (5.9 vs. 1.9%), and nonspecific external compression (5.9 vs. 1.3%). A subset analysis of patients with adhesive SBO (ASBO) showed that the MIS group tended to ( P <0.0001) have bands or simple adhesions (75.8%), whereas the TOS group predominantly had matted-type adhesions (59.4%). Furthermore, SBO in the MIS group had an acute (<3 months) or early (3-12 months) onset (64.7%), while that in the TOS group ( P <0.0001) had an intermediate or a late onset. When the surgical outcomes of SBO were evaluated, the TOS group had significantly more ( P <0.0001) blood loss and longer operation time; however, no significant difference was observed in the surgical morbidity/mortality (Clavien-Dindo classification ≧3, 11.8 vs. 14.1%, P =0.6367), hospitalization, and readmission rates between the two groups. Postoperative follow-up showed that the estimated 3-year (11.37 vs. 18.8%) and 6-year (25.54 vs. 67.4%) recurrence rates of SBO were significantly lower ( P =0.016) in the MIS group than in the TOS group. CONCLUSIONS: The wide adoption of MIS to treat primary CRC has led to a lower incidence, altered patterns, and reduced recurrence rates of SBO. Awareness of this new trend will help develop surgical techniques to prevent incomplete restoration of anatomical defects and bowel malalignments specifically associated with MIS for CRC, as well as facilitate timely and appropriate management of SBO complications whenever they occur.

Impact of positron-emission tomography on the surgical treatment of locoregionally recurrent colorectal cancer.

BACKGROUND: The effect of positron emission tomography (PET) on the surgical treatment of locoregionally recurrent colorectal cancer (LRRCRC) remains unclear and warrants further investigation. MATERIAL AND METHODS: A total of 193 patients with LRRCRC were identified from a prospectively maintained institutional database, of whom 134 LRRCRCs were deemed resectable and underwent resection with curative intent, whereas the remaining 59 LRRCRCs were unresectable. Patients with resectable LRRCRC were further classified according to whether recurrence was detected solely by PET (n = 35, PET-only group) or by a combination of computed tomography (CT)/magnetic resonance imaging (MRI) and PET (n = 99, CT/MRI/PET group). Clinicopathologic features, operative morbidity/mortality, and overall survival were compared between the patient groups based on long-term follow-up for at least 5 years. RESULTS: Patients in the PET-only group tended to have less extensive organ resection (p = 0.0074), less blood loss (p < 0.0001), and shorter operation time and hospitalization (p < 0.0001), but surgical complication and readmission rates were not significantly different (p > 0.05) compared with the CT/MRI/PET group. Although the PET-only group had significantly higher R0 resection rate (80 % vs. 54.55 %, p = 0.0079), they also had a higher risk (17.14 % vs. 2.02 %, p = 0.0011) of sham operation. The estimated 5-year and 10-year survival rates significantly decreased in order (p < 0.0001) from PET-only (85.71 % and 57.98 %) and CT/MRI/PET (41.41 % and 15.93 %) to unresectable group of patients (16.95 % and 1.88 %). Subset analysis of the CT/MRI/PET group indicated that PET improved surgical decision-making because 24 (24.2 %) LRRCRCs that manifested on CT/MRI as equivocal lesions were later confirmed by PET as resectable recurrences, while 18 (19.4 %) LRRCRCs that manifested on CT/MRI as resectable lesions were later diagnosed by PET as more disseminated unresectable recurrences and precluded futile surgery. CONCLUSION: PET alone can identify a subset (20.9 %) of LRRCRCs with less tumor burden for timely surgery; PET in combination with CT/MRI can better define the resectability of LRRCRCs. The positive impacts of PET can translate into better surgical outcomes, with enhanced safety and patient survival.

Optimized Sugar-Free Citrus Lemon Juice Fermentation Efficiency and the Lipid-Lowering Effects of the Fermented Juice.

Aging and obesity make humans more prone to cardiovascular and metabolic syndrome diseases, leading to several serious health conditions, including hyperlipidemia, high blood pressure, and sleep disturbance. This study aimed to explore the hypolipidemic effect of fermented citrus lemon juice using a hyperlipidemic hamster model. The sugar-free lemon juice's fermentation was optimized, and the characteristics of fresh and fermented lemon juice (FLJ) were evaluated and compared, which contained polyphenols and superoxide dismutase-like activity. Results showed that the absorption and utilization efficiency of FLJ was higher compared with the unfermented lemon juice. This study's prefermentation efficiency evaluation found that 21-30 days of bacterial DMS32004 and DMS32005 fermentation of fresh lemon juice provided the best fermentation benefits, and 21-day FLJ was applied as a remedy after the efficiency compassion. After six weeks of feeding, the total cholesterol (TC) and triglyceride (TG) values in the blood and liver of the FLJ treatment groups were decreased compared with the high-fat diet (HFD) group. In addition, the blood low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in the FLJ treatment groups compared with the HFD group. In contrast, the blood high-density lipoprotein (HDL-C) to LDL-C ratio increased considerably in the FLJ treatment groups, and the total to HDL ratio was significantly lower than in the HFD group. Compared with the HFD group, the TC content in the FLJ treatment groups' feces increased significantly. This study demonstrated that the sugar-free fermentation method and fermentation cycle management provided FLJ with the potential to regulate blood lipids. Further research and verification will be carried out to isolate specific substances from the FLJ and identify their mechanisms of action.

The protective effects of beta-mangostin against sodium iodate-induced retinal ROS-mediated apoptosis through MEK/ERK and p53 signaling pathways.

Previous studies have indicated that NaIO3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO3-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO3-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO3; it was mediated by significantly reduced NaIO3-upregulated ROS, cellular H2O2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO3-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO3-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.

Technical feasibility of robotic vs. laparoscopic surgery for locally advanced colorectal cancer invading the urinary bladder.

BACKGROUND: The aim of this study was to determine if robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. METHODS: We retrospectively reviewed the prospectively maintained data of patients with locally advanced colorectal cancer invading the urinary bladder undergoing robotic or laparoscopic surgery between June 2006 and November 2020. Clinicopathologic features, surgical outcomes, and oncologic efficacy were compared between patient groups of robotic or laparoscopic surgery. All patients underwent surgery with the intent of R0 resection for the primary tumor. Major surgical complications were defined as Clavien-Dindo grade ≥ III. Multivariate regression analysis was performed to identify risk factors. RESULTS: A total of 41 patients (M:F = 32:9; median age: 63 [42-88] years) were analysed; 32 underwent laparoscopic surgery and 9 underwent robotic surgery. There was no statistically significant difference between the two groups in baseline demographic and clinicopathologic features. There were no significant differences in terms of mean operative time (353.24 vs. 387.33 min), mean blood loss (315.00 vs. 171.11 mL), mean number of lymph nodes harvested (27.16 vs. 23.50), R0 resection (89.7 vs. 66.7%), conversion (12.5 vs. 11.1%), major complication rate (9.4 vs. 22.2%), mean time to flatus passage (4.8 vs. 4.1 days), mean postoperative length of hospital stay (18.9 vs. 19.8 days), 5-year disease-free survival rate (64.6 vs. 62.5%) and overall survival rate (75.3 vs. 83.3%). Multivariate analysis showed that R1 resection was the only independent prognostic factor for reduced disease-free survival (hazard ratio 21.386; 95% confidence interval 1.991-229.723; p = 0.0115). CONCLUSIONS: Robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. However, larger studies are mandatory to clarify the role of robotic surgery in such a scenario.

Particulate matter 2.5 exposure induces epithelial-mesenchymal transition via PI3K/AKT/mTOR pathway in human retinal pigment epithelial ARPE-19 cells.

Exposure to particulate matter 2.5 (PM2.5) has been linked to ocular surface diseases, yet knowledge of the molecular mechanism impacted on retina pathogenesis is limited. Therefore, the purpose of this study was to explore the effects and involved factors of PM2.5 exposure in human retinal pigment epithelial APRE-19 cells. Our data revealed a decreased cell viability and an increased migratory ability in APRE-19 cells after PM2.5 stimulation. The MMP-2 and MMP-9 protein levels were markedly increased while the MMPs regulators TIMP-1 and TIMP-2 were significantly reduced in PM2.5-exposed APRE-19 cells. PM2.5 also increased pro-MMP-2 expression in the cell culture supernatants. Additionally, PM2.5 promoted the EMT markers through the activation of PI3K/AKT/mTOR pathway. Moreover, the ICAM-1 production was also remarkably increased by PM2.5 but reduced by PI3K/AKT inhibitor LY294002 in APRE-19 cells. Taken together, these results suggest that PM2.5 promotes EMT in a PI3K/AKT/mTOR-dependent manner in the retinal pigment epithelium.

Ramucirumab plus triplet chemotherapy as an alternative salvage treatment for patients with metastatic colorectal cancer.

BACKGROUND: Ramucirumab is indicated for salvage treatment after failure of first-line treatment for metastatic colorectal cancer (mCRC). However, the application of ramucirumab at later-line treatment in real-world practice has not received much discussion. METHODS: In this retrospective study, we enrolled 70 patients with mCRC who received ramucirumab plus chemotherapy at National Taiwan University Hospital between 2018 and 2019. RESULTS: Compared with those who received third- or later-line ramucirumab treatment, patients who received second-line ramucirumab treatment had significantly longer median time to treatment discontinuation (mTTD; 6.7 vs 3.6 months, P = .004) and median overall survival (mOS; not reached vs 7.6 months, P = .009). Multivariate analyses revealed that second-line ramucirumab and triplet chemotherapy backbone were the only independent predictive factors for long mTTD and mOS. Patients who received ramucirumab with triplet chemotherapy had a significantly longer mOS than did patients who received ramucirumab with doublet chemotherapy (not reached vs 5.6 months, P = .002). Among those receiving second-line ramucirumab treatment, combination with triplet chemotherapy led to a longer mTTD than did combination with doublet chemotherapy, but the difference was non-significant (not reached vs 4.4 months, P = .108). By contrast, in patients receiving fourth- or later-line ramucirumab, combination with triplet chemotherapy led to significantly longer mTTD than did combination with doublet chemotherapy (8.0 vs 2.9 months, P = .032). CONCLUSION: Ramucirumab plus triplet chemotherapy may be an alternative regimen in patients with mCRC, particularly as a later-line treatment modality.

The necessity of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the necessity of abdominal drainage after laparoscopic appendectomy in patients with complicated appendicitis. METHODS: Patients with acute appendicitis undergoing laparoscopic appendectomy at two hospitals between January 2014 and December 2018 were retrospectively included. Complicated appendicitis was defined as the American Association for the Surgery of Trauma (AAST) grade ≥ II. The patients were classified according to the AAST grade and the indwelling of abdominal drainage. The postoperative surgical outcomes and recovery were compared among patient groups to evaluate the impact of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy. RESULTS: A total of 1241 patients was retrospectively included. Among them, there were 820 patients with simple appendicitis (AAST grade I) and 421 patients with complicated appendicitis (AAST grade ≥ II). For complicated appendicitis, the drainage group (N = 192) tended to harbor more overall complications, intra-abdominal abscess formation, time to resume a soft diet, and the postoperative length of hospitalization (P = 0.0000 for all). Multivariate logistic regression confirmed that abdominal drainage increased the risk of overall complications [Odds ratio (OR) 2.439; 95% confidence interval (CI) 1.597-3.726; P ≤ 0.0001] and failed to decrease the risk of intra-abdominal abscess formation (OR 1.655; 95% CI 0.487-5.616; P = 0.4193). Multivariate linear regression analysis also showed that the drainage group harbored longer postoperative length of hospitalization (Coefficients: 20.697; 95% CI 15.251-26.143; P < 0.0001) and time to resume a soft diet (Coefficients: 45.899; 95% CI 34.502-57.297; P < 0.0001). CONCLUSIONS: Abdominal drainage did not prevent overall complications in patients with complicated appendicitis; paradoxically, it delayed the convalescence. Our results discourage the routine use of abdominal drainage and suggest that abdominal drainage should be performed sparingly.

Robotic versus laparoscopic surgery for rectal cancer after neoadjuvant chemoradiotherapy: A propensity-score matching analysis.

BACKGROUND: We aimed to investigate the advantages of robotic versus laparoscopic surgery for rectal cancer after neoadjuvant chemoradiotherapy as these remains unclear. METHODS: We retrospectively recruited eligible patients with rectal cancer undergoing robotic or laparoscopic surgery following neoadjuvant chemoradiotherapy. We compared the surgical outcomes between patients undergoing either robotic surgery or laparoscopic surgery was based on the propensity-score matching analysis. RESULTS: A total of 171 patients were recruited, including 76 who underwent robotic surgery and 95 who underwent laparoscopic surgery. There were no significant differences in clinical and pathological characteristics between the groups after propensity-score matching (56 matched pairs). Longer operation times (324.964 ± 83.435 vs. 246.232 ± 111.324 min, p < 0.001) and more blood loss (187.679 ± 176.615 vs. 98.214 ± 107.011, p < 0.001) were observed in the robotic group. The major complication rates were similar between the treatment groups after propensity matching (p = 0.086). There were no significant differences in disease-free survival rates (p = 0.205) and overall survival rates (p = 0.837) between the groups. CONCLUSION: Robotic surgery is associated with similar technical safety and oncologic efficacy compared to laparoscopic surgery for the treatment of rectal cancer after neoadjuvant chemoradiotherapy; it is an acceptable option for patients requiring minimally invasive surgery. Nevertheless, the longer operation times and greater blood loss seen in the present study are a stark reminder that the convenience and surgical precision, on which the marketing of robotic surgery is rooted, are yet to be proven and require further investigation.

Metronomic chemotherapy with tegafur-uracil following radical resection in stage II colorectal cancer.

BACKGROUND: Stage II colorectal cancer has a relatively good prognosis. Adjuvant chemotherapy following surgery is the standard treatment for stage III colorectal cancer but is not routinely recommended for all stage II colorectal cancer patients. We aimed to evaluate the clinical outcomes, treatment results, and prognostic factors in stage II colorectal cancer patients who underwent curative surgery with/without oral tegafur-uracil (UFT). METHODS: We included stage II colorectal cancer patients who underwent curative surgery and were followed up for at least 5 years after surgery at the National Taiwan University Hospital between January 2008 and December 2012. Excluding patients receiving neoadjuvant therapy, adjuvant therapy other than UFT, and those lost follow-up, patients treated with UFT (UFT group) and those without adjuvant therapy (surgery alone group) were analyzed for their clinical outcomes and prognostic factors. RESULTS: A total of 233 patients were recruited. Of these, 104 (44.64%) underwent only surgery while 129 (55.36%) received adjuvant chemotherapy with oral UFT following surgery. Recurrence or death occurred within 5 years in 60 patients (25.75%), with a significant difference between the surgery alone (36/104, 34.62%) and UFT groups (24/129, 18.61%) (p = 0.007). The UFT group demonstrated significantly superior 5-year disease-free (p = 0.003) and overall survival rates (p = 0.001), respectively. Patient age of ≤35.3 or ˃72.7 years, UFT duration of <486.8 days, 7.1 cm < tumor size ≤13.2 cm, number of harvested lymph nodes ≤13.5, and mucinous adenocarcinoma were associated with poorer 5-year overall survival. CONCLUSION: The present data suggest that UFT following curative surgery may be associated with lower recurrence and improved survival in patients with stage II colorectal cancer.

Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells.

Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.

Cyanine-Based Polymer Dots with Long-Wavelength Excitation and Near-Infrared Fluorescence beyond 900 nm for In Vivo Biological Imaging.

Bioimaging in the near-infrared window is of great importance to study the dynamic processes in vivo with deep penetration, high spatiotemporal resolution, and minimal tissue absorption, scattering, and autofluorescence. In spite of the huge progress on the synthesis of small organic fluorophores and inorganic nanomaterials with emissions beyond 900 nm, it remains a tough challenge to synthesize semiconducting polymers with fluorescence over this region. Here, we synthesized a series of heptamethine cyanine-based polymers with both absorption and emission in the near-infrared region. We prepared these polymers as semiconducting polymer dots (Pdots) in pure water with great biocompatibility. The fluorescence quantum yield of the Pdots can be as high as 14% with a full width at half-maximum of 53 nm, and their single-particle brightness is more than 20 times higher than commercial quantum dots or ∼300 times brighter than Food and Drug Administration (FDA)-approved indocyanine green (ICG) dyes. We further demonstrated the use of cyanine-based Pdots for specific cellular labeling and long-term tumor targeting in mice. We anticipate that these cyanine-based ultrabright Pdots could open up an avenue for next generations of near-infrared fluorescent agents.

The Toldt fascia: A historic review and surgical implications in complete mesocolic excision for colon cancer.

To clarify the anatomic concept of Toldt fascia, based on the literature review and the surgical anatomic dissection using laparoscopic or robotic approach. We undertook review of the historic literature and surgical videos from 250 patients with colorectal cancer operated on laparoscopically or robotically to discuss the surgical implications of Toldt fascia in complete mesocolic excision for colon cancer. Toldt fascia, sandwiched by the overlying mesothelial layer of the mesocolon and underlying mesothelial layer of the retroperitoneum, comprised loose fibrous tissues with minute vessels inside, and was contiguous from the ileocecal mesentery radix to the upper rectum. Surgical dissection plane is readily developed within the Toldt fascia; however, any attempt to dissect along the interface between Toldt fascia and the overlying mesocolon or underlying retroperitoneum failed. Within the anatomic territory of kidney, Toldt fascia fused with Gerota fascia, and then extended in all directions: upward to the dosal surface of the duodenum, liver and pancreas; medially to fuse with the adventitia layer of the abdominal aorta; laterally, it tapered at the area below the reflection of visceral and parietal peritoneum; and downward, it became a thin membranous structure covering the gonadal vessels, ureters and retroperitoneal structures and ended at the upper rectum, where it met the junction of endopelvic fascia and proper fascia of the rectum. The present study demonstrated that Toldt fascia is a natural embryonic dissection plane for the precise conduction of complete mesocolic excision for colon cancer.