Shedding light on imaging safety: Decoding the origin of photocytotoxicity in RhB-assisted fluorescence imaging.

Photocytotoxicity represents a significant limitation in the application of dye-assisted fluorescence imaging (FI), often resulting in undesirable cellular damage or even cell death, thereby restricting their practical utility. The prevalence of Rhodamine B (RhB) in FI underscores the importance of elucidating its photocytotoxicity effects to minimize photodamage. This study identifies the primary cause of photocytotoxicity stems from the generation of cytotoxic singlet oxygen in RhB, utilizing femtosecond transient absorption spectroscopy coupled with quantum chemical calculations. The Laser power-dependent cellular viability reveals a threshold at about 50 mW cm-2, surpassing which produces pronounced photocytotoxicity in vitro and in vivo. Notably, this threshold significantly falls below the safety limits (<200 mW cm-2) for laser use in health care, implying a huge risk of photodamage. This study provides valuable insights into the photocytotoxicity and offers essential guidelines for developing safer imaging protocols.

Tetrahydrocurcumin (THC) enhanced the clearance of Cryptococcus deneoformans during infection in vivo.

Cryptococcal species often cause lung infections and are the main cause of fungal meningitis. Claudin-4 appears to be a major structural component that maintains a tight alveolar barrier and prevents fluid and electrolyte leakage into the alveolar space. We aimed to determine whether S7-tetrahydrocurcumin (THC) could clearance of C. deneoformans and regulate claudin-4 expression during C. deneoformans infection. We investigated the effect of THC on C. deneoformans infection and its possible mechanism in vivo. Transmission electron microscopy was used to observe the ultrastructure of the lung tissue and the invasion of Cryptococcus. To clarify the effect of THC, we examined claudin-4, c-Jun, and Smad2 expression. We also measured claudin-4 expression in pulmonary specimens from clinical patients. THC reduced cryptococcal cell invasion in the lungs, improved alveolar exudation, and reduced inflammation. Pretreatment with THC suppressed c-Jun and Smad2 expression, resulting in significantly increased claudin-4 levels. In contrast, the expression of claudin-4 in clinical specimens from patients with cryptococcal infection was higher than that in normal specimens. THC enhanced the clearance of C. deneoformans during infection in vivo. We investigated the expression of claudin-4 and the possible mechanism of THC against C. deneoformans infection.

Excimer-Mediated Ultrafast Intermolecular Nonradiative Decay Enables Giant Photothermal Performance for Optimized Phototheranostic.

Developing organic photothermal materials (OPMs) with high photothermal performance for phototheranostic mainly focus on the manipulation of intramolecular nonradiative (intraNR) decay, which often requires quite complicated and time-consuming molecular engineering. In addition to intraNR decay, intermolecular nonradiative (interNR) decay is equally important and more convenient in governing photothermal performance. However, controlling interNR decay remains challenging due to the limited understanding of their origin and dynamics. Here, systemic investigation of intraNR and interNR decay directs the first demonstration of simple manipulation of interNR decay to produce a giant photothermal performance for optimized phototheranostic. Among three designed polymers with varying fluorine substitution, structure-performance studies reveal a dimer-initiated interNR decay to improve photothermal performance. Dimer is formed by intermolecular CF···H hydrogen bond. This finding inspires a simple aggregation control strategy to form excited dimer, namely, excimer. It initiates an ≈100-fold enhancement in interNR decay rate over conventional intraNR decay to produce ultrahigh photothermal conversion efficiency of 81% for efficient photoacoustic imaging-guided photothermal therapy in vivo. This study provides insights into interNR decay in achieving a giant photothermal effect and paves a convenient way to develop high-performance OPMs.

Mass cytometry-based peripheral blood analysis as a novel tool for early detection of solid tumours: a multicentre study.

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

Prognostic role of the systemic immune-inflammation index in biliary tract cancers: a meta-analysis of 3,515 patients.

BACKGROUND: The systemic immune-inflammation index (SII) is an inflammatory parameter calculated as platelet count × neutrophil count/lymphocyte count in the peripheral blood. In recent years, the prognostic role of the SII in patients with biliary tract cancer (BTC) has been gradually investigated. However, the results were controversial. This meta-analysis aimed to illustrate the prognostic value of the SII in BTC. METHODS: The electronic databases of PubMed, the Web of Science, Embase, and the Cochrane Library were thoroughly retrieved up to April 15, 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the prognostic value of the SII for clinical outcomes. The association between the SII and overall survival (OS) and recurrence-free survival (RFS)/progression-free survival (PFS) was evaluated. RESULTS: Thirteen studies involving 3515 patients were included in this meta-analysis. The pooled results indicated that an elevated SII was significantly associated with poor OS (HR, 1.77; 95% CI, 1.47-2.14; p<0.001) and RFS/PFS (HR, 1.66; 95% CI, 1.38-1.99; p<0.001) in patients with BTC. Subgroup analysis stratified by country, sample size, and cutoff value showed similar results. The sensitivity analysis and publication bias test confirmed the reliability of our results. CONCLUSIONS: An elevated pretreatment SII was significantly associated with worse OS and RFS/PFS in patients with BTC. Our results suggest that the SII is a valuable and cost-effective prognostic parameter for the treatment of patients with BTC.

Histological tumor micronecrosis in resected specimens after R0 hepatectomy for hepatocellular carcinomas is a factor in determining adjuvant TACE: A retrospective propensity score-matched study.

BACKGROUND: Tumor micronecrosis is a less investigated pathological feature of hepatocellular carcinoma (HCC). This study was aimed at evaluating the value of micronecrosis for guiding adjuvant transcatheter arterial chemoembolization (TACE) in HCC management. METHODS: We retrospectively reviewed the data of patients with HCC who underwent curative liver resection in our center from 2014 to 2018. The patients were divided into micronecrosis (+) and micronecrosis (-) groups. In each group, overall survival (OS) and disease-free survival (DFS) were compared between patients who underwent adjuvant TACE and those who did not. Propensity score matching (PSM) was conducted at a ratio of 1:1 to control selection bias. Univariate and multivariate analyses were performed to determine independent prognostic factors. Mass cytometry was applied to compare the immunological status of HCCs between the two groups. RESULTS: A total of 897 patients were included, with 417 and 480 patients in the micronecrosis (+) and micronecrosis (-) groups, respectively. No significant difference was detected in baseline parameters after PSM. In the micronecrosis (+) group, patients who underwent adjuvant TACE had significant longer OS than did those who did not (P = 0.004). However, patients in the micronecrosis (-) group did not benefit from adjuvant TACE. Although adjuvant TACE prolonged the DFS of patients with severe micronecrosis (P = 0.034), it may adversely affect the DFS of patients without micronecrosis (P = 0.131). Multivariate analysis showed that TACE was an independent prognostic factor for patients with micronecrosis but not for those without micronecrosis. The abundance of exhausted and regulatory T cells was significantly higher in patients with micronecrosis. CONCLUSIONS: For HCC patients with micronecrosis, adjuvant TACE after curative resection could improve the prognosis, while its survival benefits were limited in HCC patients without micronecrosis. TACE should be selectively performed in patients with micronecrosis, especially those with an Nscore = 2. The immunosuppressive status of HCC patients with micronecrosis may explain the effectiveness of adjuvant TACE in such scinario.

Viscosity Effects on Excited-State Dynamics of Indocyanine Green for Phototheranostic.

The excited-state dynamics of indocyanine green (ICG) fundamentally determine its photophysical properties for phototheranostic. However, its dynamics are predictable to be susceptible toward intracellular viscosity due to its almost freely rotating structure, making the precise phototheranostic very challenging. Therefore, correlating the viscosity with the dynamics of ICG is of great importance and urgency for precise phototheranostic prospects. This study presents systemic investigations on the viscosity-dependent dynamics of ICG for phototheranostic. Femtosecond transient absorption (fs-TA) experiments elucidate a prolonged radiative transition (225 ps vs 152 ps) for ICG in a viscous environment, which benefits fluorescence. High viscosity remarkably extends the triplet excited-state lifetime of ICG but reduces its internal conversion (6.2 ps vs 2.2 ps). The extended triplet lifetime affords sufficient photosensitization time to enhance photodynamic therapy. A moderative internal conversion is unfavorable for heat production, resulting in inferior photothermal therapy. With this clear picture of excitation energy state dissipation in mind, we readily identified the safety laser power density for precise phototheranostic. This work provides an insightful understanding of viscosity-relevant excited-state dynamics toward phototheranostic, which is also beneficial for designing novel ICG derivatives with improved phototheranostic performance.

The effect of a simple simulator on the application of laparoscopic common bile duct exploration in a low volume center.

BACKGROUND: The purpose of this study was to investigate the effect of a simple laparoscopic common bile duct exploration (LCBDE) simulator and corresponding practicing program on the application of performing LCBDE in a low volume center. METHODS: A retrospective review was performed by analyzing data from the electronic medical record for 4118 patients with choledocholithiasis in Changxing County Hospital (Huzhou, Zhejiang, China) between January 2013 and December 2018. From January 2016, we have developed a simple LCBDE-specific simulator and corresponding practicing program in our hospital. The percentage of patients with choledocholithiasis managed by LCBDE before and after the introduction of a simple LCBDE-specific simulator and corresponding practicing program was compared. RESULTS: There were 8.9% (367/4118) patients with a diagnosis of choledocholithiasis confirmed by MRCP. Single-stage management with LC+LCBDE was performed in 23.7% (87/367) patients. Among them, 23 cases were performed between January 2013 and December 2015, and 64 cases were performed between January 2016 and December 2018. The introduction of simulator-enhanced practicing program in January 2016 has resulted in an increase in the percentage of performed LCBDE, from 12.9% to 33.9%. In addition, there was an 29.5% reduction in the mean operating time (from 193 min to 136 min) needed for LCBDE with T-tube when compared these two periods. CONCLUSIONS: LCBDE simulator can improve the application in a low volume center, and help to increase the utilization of this effective, one stage treatment for choledocholithiasis and reduce the need for costlier ERCP.

A nomogram for prediction of posthepatectomy liver failure in patients with hepatocellular carcinoma: A retrospective study.

To generate a nomogram to predict posthepatectomy liver failure (PHLF), we attempted to elucidate salient risk factors in patients with hepatocellular carcinoma (HCC).We performed a retrospective review of 665 patients with HCC who received hepatectomy in 2 academic institutions in China. Independent risk factors for PHLF were identified from putative demographic, intrinsic, biochemical, surgery-related, and volumetric data. A predictive nomogram was formulated based on relevant risk factors, and we compared this with existing models.We identified clinical signs of portal hypertension (P = .023), serum total bilirubin (P = .001), serum creatinine (P = .039), and intraoperative hemorrhage (P = .015) as being important risk factors in predicting PHLF. The nomogram had a C-index of 0.906 for the externally validated data. The nomogram displayed better predictive value than 2 of the other most cited models (C-indices of 0.641 and 0.616, respectively) in the current cohort. Additionally, we were able to patients into low- (<10%), intermediate- (10-30%), and high-risk (≥30%) groups based on the nomogram. This allows us to facilitate person-specific management.Here, we constructed a simple nomogram for prediction of PHLF in patients with HCC weighted by independent risk factors. Further prospective studies are required to confirm the predictive ability of our nomogram.

Predicting surgical site infections using a novel nomogram in patients with hepatocelluar carcinoma undergoing hepatectomy.

BACKGROUND: Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC). AIM: To identify the risk factors associated with SSI, and develop a nomogram to predict SSI among patients undergoing hepatectomy. METHODS: We retrospectively reviewed the data of patients diagnosed with HCC undergoing hepatectomy at two academic institutions in China, and evaluated the occurrence of SSI. Independent risk factors for SSI were identified using univariate and multivariate analyses. Based on these independent risk factors, a nomogram was established using the data of patients in the first institution, and was validated using data from an external independent cohort from the second institution. RESULTS: The nomogram was established using data from 309 patients, whereas the validation cohort used data from 331 patients. The operation duration, serum albumin level, repeat hepatectomy, and ASA score were identified as independent risk factors. The concordance index (C-index) of the nomogram for SSI prediction in the training cohort was 0.86; this nomogram also performed well in the external validation cohort, with a C-index of 0.84. Accordingly, we stratified patients into three groups, with a distinct risk range based on the nomogram prediction, to guide clinical practice. CONCLUSION: Our novel nomogram offers good preoperative prediction for SSIs in patients undergoing hepatectomy.

The First Report of Laparoscopic Pancreaticoduodenectomy for Primary Duodenal Carcinoma in a Patient With Situs Inversus Totalis: Report of a Rare Case.

BACKGROUND: Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery. CASE PRESENTATION: A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed. CONCLUSION: LPD is technically difficult but feasible in patients with SI.

MiR-204 inhibits hepatocellular cancer drug resistance and metastasis through targeting NUAK1.

Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.

Preoperative prediction of peripancreatic vein invasion by pancreatic head cancer.

BACKGROUND: Pancreatic adenocarcinoma is often diagnosed at an advanced stage when adjacent vascular invasion is present. Accurate evaluation of presence of vascular invasion can help guide therapy. The aim of this study was to construct a nomogram for preoperative prediction of peripancreatic vein invasion in patients with pancreatic head cancer. STUDY DESIGN: Data of patients with carcinoma head of pancreas and suspected peripancreatic invasion (n = 247) who underwent pancreatic resection with venous reconstruction between January 2012 and January 2017 at four academic institutions were retrospectively analyzed. Univariate and multivariate analyses were used to identify independent risk factors for vein invasion from among demographic, biological, conditional host-related, and anatomical data. A predictive nomogram was constructed based on the identified independent risk factors. RESULTS: The nomogram was constructed using data from 181 patients while the validation cohort consisted of 66 patients. Length of tumor contact (P = 0.031), circumferential vein involvement (P = 0.048), and venous contour abnormalities (P = 0.001) were independent predictors of venous invasion. The C-index of the model in predicting venous invasion was 0.963 for the external validation cohort. Patients could be assigned into low- (< 50%), intermediate- (50-90%), and high-risk (> 90%) groups based on the nomogram to facilitate personalized management. CONCLUSIONS: Vein invasion by pancreatic head cancer is mainly associated with anatomical factors. The nomogram for prediction of vein invasion was found to be practicable.

The role of imaging in prediction of post-hepatectomy liver failure.

Post-hepatectomy liver failure (PHLF) is not only a leading cause of mortality but also a leading cause of life-threatening complications in patients undergoing liver resection. The ability to accurately detect the emergence of PHLF represents a crucially important step. Currently, PHLF can be predicted by a comprehensive evaluation of biological, clinical, and anatomical parameters. With the development of new technologies, imaging methods including elastography, diffusion-weighted magnetic resonance imaging, and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI play a more significant role in the pre-operative prediction and assessment of PHLF. In this review, we summarize the mainstream studies, with the aim of evaluating the role of imaging and improving the clinical value of existing scoring systems for predicting PHLF.

Effects of volatile organic compounds and carbon monoxide mixtures on learning and memory, oxidative stress, and monoamine neurotransmitters in the brains of mice.

In this study, we investigated the effect of inhaled mixtures of volatile organic compounds (VOCs) and carbon monoxide (CO) on neuroethology. Fifty 6-week-old male Kunming mice were exposed in five similar static chambers; zero (control) and four different doses of VOC and CO mixtures (G1-G4) for 10 consecutive days and 2 h/day. The compounds and concentrations were as follows: formaldehyde, benzene, toluene, xylene, and CO as 0.10 + 0.11 + 0.20 + 0.20 + 10.00 mg/m3, 0.20 + 0.22 + 0.40 + 0.40 + 20.00 mg/m3, 1.00 + 1.10 + 2.00 + 2.00 + 100.00 mg/m3, and 5.00 + 5.50 + 10.00 + 10.00 + 500.00 mg/m3, respectively, which corresponded to 1, 2, 10, and 50 times the indoor air quality standard in China. Morris water maze and grip strength tests were performed during the exposure experiment. One day following the final exposure, oxidative damage levels, monoamine neurotransmitters, monoamine oxidase (MAO), and morphology of mice brain were analyzed. Escape latency, dopamine, norepinephrine (NE), and serotonin decreased significantly, while total antioxidant capacity, glutathione peroxidase, and MAO increased significantly in G3 and G4. In addition, there were morphological changes and degeneration of neurons in the dentate gyrus regions of the hippocampus in G4. Results showed that the inhaled mixtures of VOCs and CO affected learning and memory of mice. The impairment of monoamine neurotransmitter associated with MAO may be one of the mechanisms of learning and memory impairment of the mice induced by the mixtures of VOCs and CO.