Association of cancer and schizophrenia, major depression and bipolar disorder: A Mendelian randomization study.

BACKGROUND: Schizophrenia, bipolar disorder and major depression have been reported to be associated with some cancers. However, the magnitude of the causal relationship between them remains unclear. This study aims to explore the potential association between three major mental diseases and the risk of some cancers. METHODS: We performed the two-sample Mendelian randomization(MR) analysis using publicly available genome-wide association studies (GWAS) statistics to investigate the causal relationship between these three mental diseases and some common types of cancers, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, bladder cancer, prostate cancer, thyroid cancer, pancreatic cancer, malignant melanoma and glioma. We obtained genetic association estimates for schizophrenia, bipolar disorder and depression from the Psychiatric Genomics Consortium.The genetic association estimates for cancers were obtained from the UK Biobank, the MRC-IEU consortium and the GliomaScan consortium. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we detected suggestive evidence for the association between thyroid cancer and genetically predicted schizophrenia (OR = 1.543, 95% CI: 1.023-2.328, P = 0.039), and thyroid cancer and major depression (OR = 3.573, 95% CI: 1.068-11.953, P = 0.039). No evidence of causal effects of schizophrenia, major depression and bipolar disorder on other types of cancers. CONCLUSIONS: Our findings suggest the association of schizophrenia and major depression and the development of thyroid cancer.

Association of waist circumference and BMI with premature death in young and middle-aged population.

Introduction: Premature death is a global health indicator, significantly impacted by obesity, especially in young and middle-aged population. Both body mass index (BMI) and waist circumference (WC) assess obesity, with WC specifically indicating central obesity and showing a stronger relationship with mortality. However, despite known associations between BMI and premature death, as well as the well-recognized correlation between WC and adverse health outcomes, the specific relationship between WC and premature death remains unclear. Therefore, focusing on young and middle-aged individuals, this study aimed to reliably estimate independent and combined associations between WC, BMI and premature death, thereby providing causal evidence to support strategies for obesity management. Methods: This study involved 49,217 subjects aged 18-50 years in the United States from 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Independent and combined associations between WC and BMI with premature death across sex and age stratum were examined by Cox regression. Survey weighting and inverse probability weighting (IPW) were further considered to control selection and confounding bias. Robustness assessment has been conducted on both NHANES and China Health and Retirement Longitudinal Study (CHARLS) data. Results: A linear and positive relationship between WC and all-cause premature death was found in both males and females, with adjusted HRs of 1.019 (95%CI = 1.004-1.034) and 1.065 (95%CI = 1.039-1.091), respectively. Nonlinear relationships were found with respect to BMI and all-cause premature death. For females aged 36-50 with a BMI below 28.6 kg/m2, the risk of premature death decreased as BMI increased, indicated by adjusted HRs of 0.856 (95%CI = 0.790-0.927). Joint analysis showed among people living with obesity, a larger WC increased premature death risk (HR = 1.924, 95%CI = 1.444-2.564). Discussion: WC and BMI exhibited prominent associations with premature death in young and middle-aged population. Maintaining an appropriate WC and BMI bears significant implications for preventing premature death.

Construction and Identification of a Human Colorectal Adenoma Epithelial Cell Line by SV40 Large T-Antigen Transfection.

BACKGROUND: Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions. AIMS: This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection. METHODS: Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval. CONCLUSION: We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.

[Xixin Decoction regulates Th17/Treg balance and transcription factor expression in senescence-accelerated mouse-prone].

This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg) ba-lance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8) model. Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group, probiotics group, and high-, medium-, and low-dose Xixin Decoction groups, with 10 mice in each group. Ten 14-week male mice of senescence-acce-lerated mouse-resistant 1(SAMR1) served as control group. After 10 weeks of feeding, the mice were administrated with correspon-ding drugs for 10 weeks. Morris water maze test was carried out to examine the learning and memory abilities of mice. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of secretory immunoglobulin A(SIgA) in the intestinal mucosa, and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa. Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt) and forkhead box p3(Foxp3) in the mouse colon tissue. Compared with control group, the escape latency of mice in model group was significantly prolonged(P<0.01), and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P<0.01), intestinal mucosal SIgA content was significantly decreased(P<0.01), Th17 content was increased(P<0.05), Treg content was decreased(P<0.01), the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P<0.01). Compared with the model group, high-dose Xixin Decoction group improved the learning and memory ability(P<0.05 or P<0.01). Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P<0.05 or P<0.01), decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P<0.05 or P<0.01). Furthermore, they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P<0.01). In conclusion, Xixin Decoction may act on intestinal mucosal immune barrier, affect gut-brain information exchange, and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study.

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

How does the SARS-CoV-2 reinfection rate change over time? The global evidence from systematic review and meta-analysis.

BACKGROUND: There is a significant increase in the number of SARS-CoV-2 reinfection reports in various countries. However, the trend of reinfection rate over time is not clear. METHODS: We searched PubMed, Web of Science, Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang for cohort studies, case-control studies, and cross-sectional studies up to March 16, 2023, to conduct a meta-analysis of global SARS-CoV-2 reinfection rate. Subgroup analyses were performed for age, country, study type, and study population, and time-varying reinfection rates of SARS-CoV-2 were estimated using meta-regression. The risk of bias was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal tool. RESULT: A total of 55 studies involving 111,846 cases of SARS-CoV-2 reinfection were included. The pooled SARS-CoV-2 reinfection rate was 0.94% (95% CI: 0.65 -1.35%). In the subgroup analyses, there were statistically significant differences in the pooled reinfection rates by reinfection variant, and study type (P < 0.05). Based on meta-regression, the reinfection rate fluctuated with time. CONCLUSION: Meta-regression analysis found that the overall reinfection rate increased and then decreased over time, followed by a period of plateauing and then a trend of increasing and then decreasing, but the peak of the second wave of reinfection rate was lower than the first wave. SARS-CoV-2 is at risk of reinfection and the Omicron variant has a higher reinfection rate than other currently known variants. The results of this study could help guide public health measures and vaccination strategies in response to the Coronavirus Disease 2019 (COVID-19) pandemic.

Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer.

BACKGROUND: Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS: A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS: We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS: These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

[Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation].

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aß_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1ß(IL-1ß) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aß_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1ß in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

Rh-Catalyzed [2,3]-Sigmatropic Rearrangement of Alkynyl Carbenes with Allyl Sulfides to Access Sulfide-Substituted 1,5-Enynes.

This study describes the development of Rh-catalyzed [2,3]-sigmatropic rearrangement of alkynyl carbenes with allyl sulfides. The protocol exhibits equitable functional group tolerance and allows the formation of a variety of synthetically valuable sulfide-substituted 1,5-enyne products. To the best of our knowledge, this is the first example of [2,3]-sigmatropic rearrangement of alkynyl carbenes. DFT analysis supports the involvement of rhodium carbene generation, sulfonium ylides formation, and [2,3]-sigmatropic rearrangement pathway.

Impact of endogenous glucocorticoid on response to immune checkpoint blockade in patients with advanced cancer.

Background: Previous studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade. Methods: We first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed. Results: The endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC. Conclusion: Baseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.

Automated motion artifact correction for dynamic contrast-enhanced fluorescence imaging during open orthopedic surgery.

Indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can objectively assess bone perfusion intraoperatively. However, it is susceptible to motion artifacts due to patient's involuntary respiration during the 4.5-minute DCE-FI data acquisition. An automated motion correction approach based on mutual information (MI) frameby-frame was developed to overcome this problem. In this approach, MIs were calculated between the reference and the adjacent frame translated and the maximal MI corresponded to the optimal translation. The images obtained from eighteen amputation cases were utilized to validate the approach and the results show that this correction can significantly reduce the motion artifacts and can improve the accuracy of bone perfusion assessment.

Fluorescence-guided and molecularly-guided debridement: identifying devitalized and infected tissue in orthopaedic trauma.

Following orthopaedic trauma, bone devitalization is a critical determinant of complications such as infection or nonunion. Intraoperative assessment of bone perfusion has thus far been limited. Furthermore, treatment failure for infected fractures is unreasonably high, owing to the propensity of biofilm to form and become entrenched in poorly vascularized bone. Fluorescence-guided surgery and molecularly-guided surgery could be used to evaluate the viability of bone and soft tissue and detect the presence of planktonic and biofilm-forming bacteria. This proceedings paper discusses the motivation behind developing this technology and our most recent preclinical and clinical results.

Polymerization-Induced Self-Assembly: An Emerging Tool for Generating Polymer-Based Biohybrid Nanostructures.

The combination of biomolecules and synthetic polymers provides an easy access to utilize advantages from both the synthetic world and nature. This is not only important for the development of novel innovative materials, but also promotes the application of biomolecules in various fields including medicine, catalysis, and water treatment, etc. Due to the rapid progress in synthesis strategies for polymer nanomaterials and deepened understanding of biomolecules' structures and functions, the construction of advanced polymer-based biohybrid nanostructures (PBBNs) becomes prospective and attainable. Polymerization-induced self-assembly (PISA), as an efficient and versatile technique in obtaining polymeric nano-objects at high concentrations, has demonstrated to be an attractive alternative to existing self-assembly procedures. Those advantages induce the focus on the fabrication of PBBNs via the PISA technique. In this review, current preparation strategies are illustrated based on the PISA technique for achieving various PBBNs, including grafting-from and grafting-through methods, as well as encapsulation of biomolecules during and subsequent to the PISA process. Finally, advantages and drawbacks are discussed in the fabrication of PBBNs via the PISA technique and obstacles are identified that need to be overcome to enable commercial application.

Critical Evaluation of Multifunctional Betaxolol Hydrochloride Nanoformulations for Effective Sustained Intraocular Pressure Reduction.

Introduction: Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability. Methods: We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface. Results: The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy. Conclusion: The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.

Intraoperative assessment of bone viability through improved analysis and visualization of dynamic contrast-enhanced fluorescence imaging: technique report.

Bone devitalization is believed to be a critical determinant of complications such as infection or nonunion. However, intraoperative assessment of bone devitalization, particularly in open fractures and infections, remains highly subjective resulting in variation in treatment. Optical imaging tools, particularly dynamic contrast-enhanced fluorescence imaging, can provide real-time, intraoperative assessment of bone and soft tissue perfusion, which informs the tissues' ability to heal and fight infection. We describe a novel technique to apply indocyanine green-based fluorescence imaging, using a device that is frequently used in the operating room to assess skin or flap perfusion in plastic surgery, to assess bone and deep tissue perfusion in three pertinent cases: (1) a chronic infection/nonunion after a Gustilo type 3A tibia fracture (patient 1), (2) an acute Gustilo type 3C tibia open fracture with extensive degloving/soft tissue stripping (patient 2), and (3) an atrophic nonunion of the humerus (patient 3). In all three cases, fluorescence imaging (both time-specific fluorescence and maximum fluorescence) and derived kinetic maps of time-to-peak, ingress slope, and egress slope demonstrated clear spatial variation in perfusion that corresponded to the patient pathogenesis. The impact of this information on patient outcome will need to be evaluated in future clinical trials; however, these cases demonstrate in principle that optical imaging information has the potential to inform surgical practice, reduce the variation in treatment, and improve outcomes observed in these challenging patients.

Serum amino acids quantification by plasmonic colloidosome-coupled MALDI-TOF MS for triple-negative breast cancer diagnosis.

Triple-negative breast cancer (TNBC) is characterized with high diffusion, metastasis and recurrence. The early treatment and early diagnosis of TNBC are highly important for the survival of TNBC patients. Nevertheless, traditional methods for TNBC diagnosis, i.e. imaging examinations and tissue biopsy, cannot achieve early diagnosis, are invasive and associated with the risk of arousing tumor spreading. Herein, we developed colloidosomes-coupled matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify free serum amino acids for the diagnosis of TNBC. Gold nanoparticles (AuNPs) were used to form water-in-oil colloidosomes and to encapsulate deproteinated serum for MALDI-TOF MS analysis. With small sample spot size (200-300 µm) and densely packed AuNPs monolayer, the dried sample spot from colloidosomes can facilitate MALDI-TOF MS analysis of small molecule metabolites with high sensitivity, high reproducibility and good quantification performance. We used the method to quantify free amino acids in human serum. A cohort of 30 TNBC patients, 30 breast lump patients and 30 healthy controls were recruited for the study. It was found that the concentrations of free amino acids in TNBC patients were significantly lower than that of heathy controls, and the concentrations were also significantly different from that of breast lump patients. Based on the quantities of serum free amino acids, we have built a machine learning-based classification model to differentiate TNBC patients from the controls, including healthy controls and breast lump patients, and the sensitivity, specificity and accuracy were 95%, 100% and 97%, respectively. The assay consumes less than 1 â€‹µL serum per analysis, and takes only minutes to analyze a sample. With the advantages of low cost, low sample consumption, high throughput in analysis and high accuracy in identification, the non-invasive liquid biopsy method is promising to be applied to clinical diagnosis of TNBC.

Rh-Catalyzed Coupling Reactions of Fluoroalkyl N-Sulfonylhydrazones with Azides Leading to α-Trifluoroethylated Imines.

Herein we describe the pioneering Rh-catalyzed coupling reactions of a fluoroalkyl carbene with azides to access α-trifluoroethylated imines, where fluoroalkyl N-sulfonylhydrazones are used as fluoroalkyl diazo surrogates. Remarkably, using TMSN3 as the N source, two C-N bond formation products were obtained. Furthermore, the α-trifluoroethylated imine products could be easily reduced to the corresponding N-trifluoroethylated anilines. Experimental results and theoretical calculations justify a stepwise reaction pathway involving the formation of rhodium carbene, the addition of HN3, and C═N bond formation.

Silver-Catalyzed Vinylcarbene Insertion into C-C Bonds of 1,3-Diketones with Vinyl-N-triftosylhydrazones.

We describe the silver-catalyzed formal insertion of a vinylcarbene into unstrained C(CO)-C bonds of 1,3-diketones using vinyl-N-triftosylhydrazones as vinylcarbene precursors. This method allows the rapid synthesis of otherwise inaccessible 2-vinyl-substituted 1,4-diketones from relatively simple substrates. This mild catalytic protocol exhibits a good functional group tolerance and substrate scope and allows for good chemoselectivity control. The preliminary theoretical calculations suggest that the reaction proceeds through a stepwise enol cyclopropanation/retro-aldol pathway.

Dynamic contrast-enhanced fluorescence imaging compared with MR imaging in evaluating bone perfusion during open orthopedic surgery.

ICG-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) and intraoperative DCE- magnetic resonance imaging (MRI) have been carried out nearly simultaneously in three lower extremity bone infection cases to investigate the relationship between these two imaging modalities for assessing bone blood perfusion during open orthopedic surgeries. Time-intensity curves in the corresponding regions of interest of two modalities were derived for comparison. The results demonstrated that ICG-based DCE-FI has higher sensitivity to perfusion changes while DCE-MRI provides superior and supplemental depth-related perfusion information. Research applying the depth-related perfusion information derived from MRI to improve the overall analytic modeling of intraoperative DCE-FI is ongoing.