Impact of Removal of Lymph Nodes on Survival in Stage I-III Gastric Signet-Ring Cell Cancer: The More, the Better?

BACKGROUND: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs. METHODS: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center database were identified. Clinicopathological characteristics were retrospectively collected, and optimal cutoff values of ELNs were calculated by using X-tile. The impact of different ELNs on overall survival (OS) was compared by using Kaplan-Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated by using restricted cubic splines (RCSs). RESULTS: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (hazard ratio = 0.56, 95% confidence interval 0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm, and TNM III stage was still observed. The RCS regression model showed a U-shaped dose-response nonlinear relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs. CONCLUSIONS: A U-shaped, nonlinear correlation with inflection points of 44-52 ELNs between ELNs and prognosis in GSRCC was identified.

PhenoAge and PhenoAgeAccel in the context of dyslipidemia: association with stroke and potential as a new predictor in the US general population.

BACKGROUND: The challenges posed by an aging society are increasingly recognized, particularly regarding the potential impacts of high-fat diets and the trend toward younger ages of disease onset. The purpose of this study was to clarify the relationships between the prevalence of stroke in the general US population and PhenoAge (PA) and PhenoAgeAccel (PAA). METHODS: Key methods included a correlation heatmap to explore linear relationships between some of the variables and weighted multivariable logistic regression to assess associations between PA, PAA, and stroke. Restricted cubic spline (RCS) analysis was used to investigate nonlinear relationships and dose-response effects. The ability of the PAA to predict stroke risk was assessed by a nomogram model and a receiver operating characteristic curve. RESULTS: After adjusting for confounding variables, both continuous and categorical PA and PAA were significantly associated with stroke prevalence. RCS analysis revealed a significant nonlinear relationship between PA and stroke prevalence. Further subgroup RCS analysis indicated that maintaining PA below 31.6 could provide greater benefits across all races and genders, specifically for individuals aged 40-80 years and those who are overweight or obese. CONCLUSION: This study highlights the importance of stroke prevention in overweight and obese populations. Monitoring intermediary factors such as high-density lipoprotein cholesterol and waist circumference may reduce stroke risk. Additionally, PA and PAA may serve as novel markers for stroke, offering new directions for health management in an aging society.

The effects of different types of Tai Chi exercises on preventing falls in older adults: a systematic review and network meta-analysis.

OBJECTIVES: Few studies comparing the effects of different types of Tai Chi exercises on preventing falls in older adults. We compared the effects for finding an optimal intervention. METHODS: We searched 12 databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and so on, from their inception to January 13, 2023. Randomized controlled trials incorporating different types of Tai Chi for preventing falls in older adults were included. The outcome measures were the incidence of falls and Berg Balance Scale (BBS). Network meta-analysis (NMA) was conducted using Stata 15.1 based on a frequentist framework. RESULTS: Seventeen trials were eligible, including 3470 participants and four types of Tai Chi. They were 24-form simplified Tai Chi (24-form), Yang style Tai Chi (Yang style), Sun style Tai Chi (Sun style) and Tai Chi exercise program (TCEP). In paired meta-analysis, for incidence of falls, 24-form (Relative Risk (RR) = 0.59, 95% confidence interval (CI) [0.40, 0.86]) was more efficient than the control group. For BBS outcome, 24-form (MD (mean difference) = 2.32, 95% CI [1.42, 3.22]) was better than the control group. In the NMA, the results of incidence of falls were as follows: 24-form > Yang style > Sun style > control > TCEP. The rank probability of BBS was as follows: 24-form > TCEP > Yang style > control. CONCLUSION: Among the four types of Tai Chi studied, the 24-form simplified Tai Chi has shown better efficacy than other types.

Nonbasic Synthesis of Thioethers via Nickel-Catalyzed Reductive Thiolation Utilizing NBS-Like N-Thioimides as Electrophilic Sulfur Donors.

The nonbasic synthesis of unsymmetrical thioethers via nickel-catalyzed reductive thiolation between aryl(hetero) iodides and N-thioimides is illustrated. N-Bromosuccinimide (NBS)-like N-thioimides were found quite reactive toward thiolation with carbon electrophiles, and a series of structurally varied thioethers were successfully prepared under mild reaction conditions. The transformation was featured with the new application of the NBS-like reagents, good functional group tolerance, and late-stage modification of biologically active scaffolds, thus providing an expeditious and efficient platform to construct polyfunctional thioethers.

PNP-type ligands enabled copper-catalyzed N-formylation of amines with CO2 in the presence of silanes.

The sustainable catalytic transformation of carbon dioxide into valuable fine chemicals with high efficiency is a global challenge as although CO2 is an abundant, nontoxic, and sustainable carbon feedstock it is also the most important factor behind the Greenhouse Effect. We describe herein a PNP-type ligand-enabled copper-catalyzed N-formylation of amines utilizing CO2 as the building block in the presence of hydrosilane as the reductant. Our current protocol featured newly synthesized PNP-type ligands with broad substrate scope under mild reaction conditions.

CT-based radiographic measurements and effectiveness estimates of full-endoscopic surgery in thoracic myelopathy caused by ossification of ligamentum flavum.

BACKGROUND: Evaluate the effectiveness of posterior percutaneous full-endoscopic technique for patients with thoracic myelopathy caused by ossification of ligamentum flavum (TOLF). METHODS: A prospective study was conducted for 16 patients with TOLF, who were treated with posterior endoscopic technique from 2017 to 2019. The sagittal and cross-sectional CT images are used to measure the area of ossified ligamentum and evaluate the decompression of surgery, respectively. The effectiveness was evaluated with visual analog scale (VAS), modified Japanese Orthopedic Association scale (mJOA), The Oswestry Disability Index (ODI), and Macnab efficacy evaluation. RESULTS: The average area of TOLF on sagittal and cross-sectional CT images in the 16 patients was (116.62 ± 32.72) mm2 and (141.59 ± 27.25) mm2 preoperatively, (15.99 ± 12.54) mm2 and (11.72 ± 8.64) mm2 at 3 days after the operation, (16.78 ± 11.49) mm2 and (10.82 ± 7.57) mm2 postoperative 1 year, respectively. The invasive proportion of spinal canal at preoperative sagittal and cross-sectional CT images was (48.10 ± 10.04) % and (57.58 ± 11.37) %, which decreased to (6.83 ± 4.48) % and (4.40 ± 3.01) % at the final follow-up. The average score of mJOA, VAS and ODI improved. The excellent and good rate was 87.50% according to Macnab evaluation. Compared with preoperative, differences in areas of TOLF, proportions of spinal canal, and clinical assessments of postoperative 3 days and 1 year were all statistically significant. Two cases of dural tear were observed. CONCLUSION: Endoscopic surgery has a good clinical effect on TOLF, which has the advantage of less trauma to the paraspinal muscles and no impact on the spinal structure. The CT-based radiographic measurements can quantitatively evaluate the degree of spinal canal stenosis in TOLF.

Research Progress on Nanoplatforms and Nanotherapeutic Strategies in Treating Glioma.

Glioma is the most common and aggressive primary intracranial tumor within the central nervous system. The blood-brain barrier (BBB) has been a great hurdle for an effective glioma treatment. To effectively treat glioma, various strategies have been applied to deliver drugs to the brain by crossing the BBB. Nanocarrier-mediated drug delivery is emerging as an effective and noninvasive system to treat glioma, showing great potential in glioma therapy. In this review, we will provide a comprehensive overview on nanocarrier-mediated drug delivery and related glioma therapy. Following an initial overview of the BBB and blood-brain-tumor barrier (BBTB) structure and characteristics, nanocarrier-mediated drug delivery strategies (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, biomimetic nanoparticles, and exosomes) for crossing the BBB are discussed. Finally, nanotherapeutic techniques (imaging-mediated chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, immunotherapy, ferroptosis therapy, sonodynamic therapy, chemodynamic therapy, and combination therapy) in treating glioma are summarized. In addition, this review provides some perspectives on the clinical applications of nanomedicines.

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines That Furnish Allylic Amines.

We introduce a new reagent class, 2-azatrienes, as a platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by a diastereodivergent synthesis of syn- and anti-1,2-diamines through their Cu-bis(phosphine)-catalyzed reductive couplings with imines. With Ph-BPE as the supporting ligand, anti-diamines are obtained (up to 91% yield, >20:1 dr, and >99:1 er), and with the rarely utilized t-Bu-BDPP, syn-diamines are generated (up to 76% yield, 1:>20 dr, and 97:3 er).

Neuroprotective effects of blueberry anthocyanins against perfluorooctanoic sulfonate on planarian Dugesia japonica.

In this study, the planarian Dugesia japonica was exposed to perfluorooctane sulfonate (PFOS) and blueberry anthocyanins (ANT) for 1-10 days to investigate the protective effects of ANT on neurotoxicity and DNA damage induced by PFOS. The expression of neural related genes (Djnlg, DjFoxD, DjFoxG, DjotxA, and DjotxB) in D. japonica following exposure was determined using quantitative real-time PCR (qPCR). Immunofluorescence was performed to determine the alterations in neural morphology. In addition, ELISA kits were used to measure level of the neurotransmitters Dopamine (DA), serotonin (5-HT) and γ-aminobutyric acid (GABA). Furthermore, single cell gel electrophoresis was measured to analyze DNA damage. In this study, PFOS treatment induced neural morphology defects, alterations in neural-related gene expression, alterations in neurotransmitter levels, and DNA damage. However, co-exposure to ANT and PFOS mitigated the damage to D. japonica induced by PFOS. Restoration of neurotransmitter contents and neural related genes expression were observed in planarians following co-application of ANT and PFOS, immunofluorescence showed that nerve morphology almost recovered, and DNA damage was decreased. The results of this study showed that ANT may have a protective effect against PFOS induced neurotoxicity and DNA damage.

Enantioselective Synthesis of anti-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines.

Here we report highly efficient and chemoselective azadiene-imine reductive couplings catalyzed by (Ph-BPE)Cu-H that afford anti-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products' diamines are easily differentiable, facilitating downstream synthesis.

2-Azadienes as Reagents for Preparing Chiral Amines: Synthesis of 1,2-Amino Tertiary Alcohols by Cu-Catalyzed Enantioselective Reductive Couplings with Ketones.

We introduce a new strategy for synthesis of chiral amines: couplings of α-aminoalkyl nucleophiles generated by enantioselective migratory insertion of 2-azadienes to a Cu-H. In this report, we demonstrate its application in catalytic reductive coupling of 2-azadienes and ketones to furnish 1,2-amino tertiary alcohols with vicinal stereogenic centers.

Shelf-stable electrophilic reagents for trifluoromethylthiolation.

Fluorine, which is the most electronegative element and has a small atomic radius, plays a key role in pharmaceutical, agrochemical, and materials sciences. One of the fluoroalkyl groups, the trifluoromethylthio group (CF3S-), has been well-recognized as an important structural motif in the design of lead compounds for new drug discovery because of its high lipophilicity (Hansch lipophilicity parameter π = 1.44) and strong electron-withdrawing properties, which could improve the drug molecule's cell-membrane permeability and enhance its chemical and metabolic stability. While classic methods for the preparation of trifluoromethylthiolated compounds typically involve halogen-fluorine exchange reactions of polyhalogenomethyl thioethers or trifluoromethylation of sulfur-containing compounds under harsh reaction conditions, an alternative but more attractive strategy is direct trifluoromethylthiolation of the substrate at a late stage by employing an electrophilic trifluoromethylthiolating reagent. Although several electrophilic trifluoromethylthiolating reagents have been reported previously, these reagents either require a strong Lewis acid/Brønsted acid as an activator or suffer from a toxic nature or limited substrate scope. To address these problems, in late 2011 we initiated a project with the aim to develop new, shelf-stable, and highly reactive electrophilic trifluoromethylthiolating reagents that could easily install the trifluoromethylthio group at the desired positions of the drug molecule at a late stage of drug development. Inspired by the broad reactivity of the hypervalent iodine reagent, we initially discovered a highly reactive trifluoromethylthiolating reagent, trifluoromethanesulfenate 1a. Structure-reactivity studies disclosed that the iodine atom of reagent 1a does not play an important role in this reagent's reactivity. Consequently, a simplified second-generation electrophilic reagent, trifluoromethanesulfenate 1b, was developed. In parallel, we developed another shelf-stable, highly reactive electrophilic reagent with a broad substrate scope, N-trifluoromethylthiosaccharin (2). In this Account, we mainly describe our discovery of these two different types of electrophilic trifluoromethylthiolating reagents, trifluoromethanesulfenates 1a and 1b and N-trifluoromethylthiosaccharin 2. Systematic studies showed that both types of reagents are highly reactive toward a wide range of nucleophiles, yet the substrate scopes of these two different types of reagents are complementary. In particular, reagents 1a and 1b are more reliable in transition-metal-catalyzed reactions such as copper-catalyzed trifluoromethylthiolation of aryl/vinyl/alkylboronic acids and silver-catalyzed decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids as well as in the organocatalytic asymmetric trifluoromethylthiolation of ß-keto esters and oxindoles. Reagent 2 is more electrophilic than reagents 1a and 1b and is more efficient for direct trifluoromethylthiolation with nucleophiles such as alcohols, amines, thiols, and electron-rich arenes. The ease in preparation, broad scope, and mild reaction conditions make reagents 1a, 1b, and 2 very attractive as general reagents that allow rapid installation of the trifluoromethylthio group into small molecules.

PhSO2 SCF2 H: A Shelf-Stable, Easily Scalable Reagent for Radical Difluoromethylthiolation.

A new shelf-stable and easily scalable difluoromethylthiolating reagent S-(difluoromethyl) benzenesulfonothioate (PhSO2 SCF2 H) was developed. PhSO2 SCF2 H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl-difluoromethylthio difunctionalization of alkenes under mild reaction conditions.

Structure-reactivity relationship of trifluoromethanesulfenates: discovery of an electrophilic trifluoromethylthiolating reagent.

A family of electrophilic trifluoromethanesulfenates was prepared. Structure-reactivity relationship studies showed that the substituted groups on the aryl ring of the trifluoromethylthiolating reagent did not have an obvious influence on their reactivities. A simplified electrophilic trifluoromethylthiolating reagent 1c was then identified that can react with a wide range of nucleophiles such as Grignard reagents, arylboronic acids, alkynes, indoles, ß-ketoesters, oxindoles, and sodium sulfinates under mild reaction conditions. A variety of functional groups were tolerated under these conditions.

Silver-catalyzed decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids in aqueous emulsion.

A silver-catalyzed decarboxylative trifluoromethylthiolation of secondary and tertiary carboxylic acids under mild conditions tolerates a wide range of functional groups. The reaction was dramatically accelerated by its performance in an aqueous emulsion, which was formed by the addition of sodium dodecyl sulfate to water. It was proposed that the radical, which was generated from the silver-catalyzed decarboxylation in the "oil-in-water" droplets, could easily react with the trifluoromethylthiolating reagent to form the product.

A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors. Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use. Results: Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/. Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.

Biological Evaluation of Lysionotin: a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma.

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.

Efficacy of Baduanjin for obesity and overweight: a systematic review and meta-analysis.

Background: According to data from the World Health Organization (WHO), there is a significant public health issue regarding the increasing number of individuals affected by obesity and overweight on an annual basis. Therefore, it is imperative to urgently identify interventions that can effectively control and improve this condition. Baduanjin, as a medium-intensity exercise, appears a suitable approach for weight reduction among individuals with obesity. This paper aimed to provide a systematic review and meta-analysis of the efficacy of Baduanjin in addressing obesity and overweight, with the ultimate goal of assisting individuals with obesity in finding an effective, safe, and engaging method for weight reduction. Methods: We conducted a comprehensive search of multiple databases including PubMed, Cochrane Library, Web of Science, Embase, The China National Knowledge Infrastructure (CNKI), The Chinese Scientific Journal Database (VIP), The Chinese Biomedical Literature Database (CBM), and WanFang Database to identify relevant articles published from the inception of each database until September 2023. Specifically, we focused on randomized controlled trials (RCTs) investigating the effects of Baduanjin on weight reduction. Data from these studies were extracted and analyzed using appropriate statistical methods. In cases where there was no significant heterogeneity (I 2 < 50%, p > 0.1), we employed a fixed effects model for data synthesis; otherwise, a random effects model was selected. Funnel plots were used to assess publication bias, and the mean difference (MD) was reported as an indicator of treatment group differences. Results: A total of 420 participants were included in 10 studies. The MD results of the experimental group when compared with the control group were -3.69 (95%CI = -4.97 to -2.40, p < 0.001) for body weight (BW), -5.42 (95%CI = -6.56 to -4.28, p < 0.001) for body mass index (BMI), -1.36 (95%CI = -1.76 to -0.96, p < 0.001) for waist circumference (WC), -3.40 (95%CI = -4.43 to -2.37, p < 0.001) for hip circumference (HC), and -0.03 (95%CI = -0.04 to -0.02, p > 0.1) for the waist-to-hip ratio (WHR). All of the values in the experimental group showed significant difference. The results of the Egger's test (t = 1.43, p = 0.190) suggest that there was no substantial bias present within the data analysis process. The safety profile revealed no adverse events reported across all 10 studies. Conclusion: Baduanjin could be effective in reducing weight, and the practice of Baduanjin has the potential to regulate BW, BMI, WC, HC, and WHR. However, further well-designed RCTs are still necessary to provide more robust evidence in the future. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024513789.