Identifying optimal candidates for post-TIPS patients with HCC undergoing TACE: a multicenter observational study.

OBJECTIVE: To develop a prognostic model for post-transjugular intrahepatic portosystemic shunt (TIPS) patients with hepatocellular carcinoma (HCC) beyond the Milan criteria treated by transarterial chemoembolization (TACE). DESIGN: Between January 2013 and January 2020, 512 patients with HCC beyond the Milan criteria who underwent TACE after TIPS were retrospectively recruited from 15 tertiary centers. Patients were randomly sorted into a training set (n = 382) and a validation set (n = 130). Medical data and overall survival were assessed. A prediction model was developed using multivariate Cox regression analyses. Predictive performance and discrimination were evaluated and compared with other prognostic models. RESULTS: Vascular invasion, log10(AFP), 1/creatinine, extrahepatic spread, and log10(ALT) were the most significant prognostic factors of survival. These five parameters were included in a new VACEA score. This score was able to stratify patients in the training set into four distinct risk grades whose median overall survival were 25.2, 15.1, 8.9, and 6.2 months, respectively. The 6-month, 1-year, 2-year, and 3-year AUROC values and C-index of the VACEA model were 0.819, 0.806, 0.779, 0.825, and 0.735, respectively, and higher than those of other seven currently available models in both the training and validation sets, as well as in different subgroups. CONCLUSION: The VACEA score could stratify post-TIPS patients with HCC beyond the Milan criteria treated by TACE and help to identify candidates who benefit from this treatment. KEY POINTS: • Vascular invasion, AFP, creatinine, extrahepatic spread, and ALT were independent significant prognostic factors of survival for HCC patients who underwent TACE after TIPS. • Our new model, named VACEA score, can accurately predict prognosis at the individual level and stratify patients into four distinct risk grades. • The VACEA model showed better prognostic discrimination and calibration than other current TACE-/TIPS-specific models Graphical abstract.

Laboratory risk factors for coexistent primary biliary cholangitis in patients with Sjögren's syndrome: a retrospective study.

BACKGROUND: Limited research exists on the laboratory characteristics of coexistent primary biliary cholangitis (PBC) and Sjögren's syndrome (SS). This study aimed to investigate the laboratory risk factors for the coexistence of PBC in patients with SS. METHODS: Eighty-two patients with coexistent SS and PBC (median age 52.50 years) and 82 age- and sex-matched SS controls were retrospectively enrolled between July 2015 and July 2021. The clinical and laboratory characteristics of the two groups were compared. Laboratory risk factors for the coexistence of PBC in patients with SS were analyzed using logistic regression analysis. RESULTS: Both groups had a similar prevalence of hypertension, diabetes, thyroid disease, and interstitial lung disease. Compared with the SS group, patients in the SS + PBC group had higher levels of liver enzymes, immunoglobulins M (IgM), G2, and G3 (P < 0.05). The percentage of patients with an antinuclear antibody (ANA) titre > 1:10000 in the SS + PBC group was 56.1%, higher than that in the SS group (19.5%, P < 0.05). Additionally, cytoplasmic, centromeric, and nuclear membranous patterns of ANA and positive anti-centromere antibody (ACA) were observed more frequently in the SS + PBC group (P < 0.05). Logistic regression analysis showed that elevated IgM levels, high ANA titre, cytoplasmic pattern, and ACA were independent risk factors for PBC coexistence in SS. CONCLUSIONS: In addition to established risk factors, elevated IgM levels, positive ACA, and high ANA titre with cytoplasmic pattern provide clues to clinicians for the early screening and diagnosis of PBC in patients with SS.

Drug-eluting beads TACE is safe and non-inferior to conventional TACE in HCC patients with TIPS.

OBJECTIVES: This study aims to compare the safety and effectiveness between transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and conventional TACE (cTACE) using lipiodol-based regimens in HCC patients with a transjugular intrahepatic portosystemic shunt (TIPS). METHODS: This retrospective study included patients with patent TIPS who underwent TACE from January 2013 to January 2019 that received either DEB-TACE (DEB-TACE group, n = 57) or cTACE (cTACE group, n = 62). The complications, liver toxicity, overall survival (OS), time to progression (TTP), and objective response rate (ORR) were compared between the groups. RESULTS: Altogether, 119 patients (50 ± 11 years, 107 men) were evaluated. The incidence of adverse events, including abdominal pain within 7 days (45.6% vs 79.0%, p < 0.001) and hepatic failure within 30 days (5.3% vs 19.4%, p = 0.027), were significantly lower in the DEB-TACE group than in the cTACE group. Compared to the cTACE group, the DEB-TACE group also showed mild liver toxicities in terms of increased total bilirubin (8.8% vs 22.6%), alanine aminotransferase (5.3% vs 21.0%), and aspartate aminotransferase (10.5% vs 29.0%) levels. The DEB-TACE group had better ORR than the cTACE group (70.2% vs 50.0%). The median OS and TTP were longer in the DEB-TACE group (11.4 vs 9.1 months, hazard ratio [HR] = 2.46, p < 0.001; 6.9 vs 5.2 months, HR = 1.47, p = 0.045). Multivariable analysis showed that α-fetoprotein levels, Barcelona clinic liver cancer stage, and treatment allocation were independent predictors of OS. CONCLUSION: DEB-TACE is safe and effective in HCC patients with a TIPS and is potentially superior to cTACE in terms of complications, liver toxicities, OS, TTP, and ORR. KEY POINTS: • DEB-TACE is safe and effective in HCC patients after a TIPS procedure. • DEB-TACE improves overall survival, objective response rate, and liver toxicities and is non-inferior to cTACE in terms of time to progression. • DEB-TACE might be a potential new therapeutic option for HCC patients with TIPS.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Combined Use of Transjugular Intrahepatic Portosystemic Shunt and Transarterial Chemoembolization in the Treatment of Esophageal and Gastric Variceal Bleeding: A Retrospective Study of 80 Patients with Hepatocellular Carcinoma and Portal Hypertension.

BACKGROUND The main cause of death in patients with hepatocellular carcinoma (HCC) with portal hypertension is esophageal and gastric variceal bleeding caused by severe portal hypertension; therefore, the treatment of portal hypertension is particularly important to prolong the survival of patients. The therapeutic efficacy and safety of transarterial chemoembolization (TACE) combined with a transjugular intrahepatic portosystemic shunt (TIPS) for HCC with esophageal and gastric variceal bleeding has been rarely reported. The aim of this study was to analyze the clinical efficacy of TIPS combined with TACE in the treatment of HCC with esophageal and gastric variceal bleeding. MATERIAL AND METHODS A total of 80 patients with HCC with esophageal and gastric variceal bleeding from July 2015 to November 2019 were retrospectively investigated. Clinical outcomes, biochemical indexes, and complications were compared between TIPS plus TACE and endoscopy plus TACE treatments. RESULTS Gastrointestinal rebleeding and adverse reactions (P<0.05) after TIPS combined with TACE were lower than that after endoscopy combined with TACE treatment. Furthermore, TIPS plus TACE had superior clinical outcomes than endoscopy plus TACE, which was associated with promising progression-free survival, overall survival, objective response rate, and disease control rate, and improved liver function. CONCLUSIONS TIPS combined with TACE was better than endoscopy combined with TACE in the treatment of patients with HCC and esophageal and gastric variceal bleeding. TIPS combined with TACE had a better therapeutic effect on improving liver function and prolonging patient survival time.

[Determination of caffeine content in Ginkgo Folium by ultra high performance liquid chromatography-triple quadrupole mass spectrometry].

In this experiment, an ultra-high performance liquid chromatographytandem triple quadrupole mass spectrometry was established for the determination of caffeine in commercially available Ginkgo Folium. The samples were extracted by ultrasonic method with methanol, and separated on Waters CORTECS T3 column(2.1 mm×100 mm, 2.7 µm), with mobile phase of 0.1% formic acid solution-0.1% formic acid acetonitrile solution for gradient elution, at flow rate of 0.3 mL·min~(-1); column temperature of 30 ℃, and injection volume of 2 µL. Mass spectrometry was conducted at ESI~+ multiple reaction monitoring(MRM) mode; quantitative analysis was conducted with external standard method. The results showed that in the range of 0.099 6-9.96 ng·mL~(-1), there was a good linear relationship between the mass concentration of caffeine and the peak area, R~2=0.999; the average recovery was 84.51%, with RSD of 6.2%. The results of precision, repeatability and stability showed that the RSD was 5.1%, 5.9%, 7.2%, respectively. The content range of caffeine in 10 batches of Ginkgo Folium was 1.52-60.86 µg·kg~(-1). In conclusion, this method is accurate, reliable and reproducible, which provides a reference for the safety study of Ginkgo Folium.

[Effect of heavy metal lead on anticoagulant activity of leech based on label-free quantitative proteomics].

Whitmania pigra is the most widely distributed species of leeches in the market. In this study, the effect of heavy metal lead pollution on the anticoagulant activity of Wh. pigra was studied and the potential mechanism was explored. Pb(NO_3)_2 was used to contaminate the breeding soil which was then used to rear Wh. pigra for 50 days(lead-contaminated group, LC group), and meanwhile the blank control group(CG group) was set. Proteins were extracted from the obtained leech samples, and the differentially expressed proteins between LC and CG groups were analyzed by label-free proteomics technology. In this study, a total of 152 differentially expressed proteins were screened out, of which 93 proteins were up-regulated and 59 proteins were down-regulated in LC group. Bioinformatics analysis showed that the biological processes enriched with the differentially expressed proteins were mainly vesicle-mediated transport and transport positive regulation; the enriched cell components were mainly endocytosis vesicles and apical plasma membrane; the enriched molecular functions mainly included carbohydrate binding. The differentially expressed proteins were enriched in 76 KEGG pathways, which mainly involved metabolic pathways, biosynthesis of secondary metabolites, and bacterial invasion of epithelial cells. In this study, two differentially expressed proteins with Antistasin domain were presumed, which provides reference for further exploring the regulatory mechanism and signal transduction underlying the effect of lead pollution on the anticoagulant activity of leech.

Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients.

OBJECTIVES: IgG4-related disease (IgG4-RD) has recently been recognized as a fibro-inflammatory condition featuring tumefactive lesions in multiple organs, and the salivary gland is one of the most commonly involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesions (IgG4-RD SG+) and salivary-gland-free IgG4-RD (IgG4-RD SG-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2006 and May 2018. RESULTS: Among 428 patients, 249 had salivary glands that were affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. The IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, the IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney and aorta were more prominent in the IgG4-RD SG- group. In addition, the serum IgG4 level, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in the IgG4-RD SG+ group, while elevated ESR, CRP and positive ANA were more common in the IgG4-RD SG- group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Postintervention Interleukin-6 (IL-6) Level, Rather than the Pretreatment or Dynamic Changes of IL-6, as an Early Practical Marker of Tumor Response in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

BACKGROUND: The aim of this study was to determine the potential prognostic roles of the perioperative interleukin-6 (IL-6) level and its dynamic changes in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: Sixty patients with hepatitis B virus-associated HCC receiving TACE were enrolled in the study. Serum IL-6 levels were determined at baseline and 1 day after TACE by immunoassay. Response to TACE was evaluated after a 4-6-week interval. Factors associated with tumor response were analyzed by univariate and multivariate analysis in a Cox regression model. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of the included variables on tumor response in patients with HCC undergoing TACE. RESULTS: The serum IL-6 level was significantly elevated 1 day after TACE. Patients in the low postintervention IL-6 level group had a high probability of achieving an objective response (OR) (66.7% vs. 18.8%, p = .021). Post-TACE IL-6 level (≤12.7 pg/mL) and post-/pre-TACE neutrophils ratio (>2.47) were independently correlated with OR after TACE. ROC curve analysis showed that a combined index based on those two factors exhibited optimal predictive power of tumor response among all the included variables (area under the curve = 0.740, 95% confidence interval: 0.601-0.879). Additionally, high post-TACE plasma IL-6 level was associated with maximum tumor size, vascular invasion, post-TACE aspartate aminotransferase, and Barcelona Clinic Liver Cancer stage. CONCLUSION: Our study suggests that the post-treatment serum IL-6 level, rather than pretreatment or dynamic changes of IL-6, serves as a powerful predictor for tumor response. These findings provide evidence to help discriminate between patients who will particularly benefit from TACE and those who require more personalized therapeutic regimens and rigorous surveillance. IMPLICATIONS FOR PRACTICE: Transarterial chemoembolization (TACE) is a major therapeutic regimen for advanced hepatocellular carcinoma. Thus, identification of early practical markers of tumor response to TACE is of high importance. This study indicated that the post-treatment serum interleukin-6 (IL-6) level, rather than the pretreatment or dynamic changes of IL-6, serves as a powerful predictor for tumor response. A combined index based on the post-TACE IL-6 level and post-/pre-TACE neutrophils ratio is optimal for predetermining an objective response after TACE, which may be helpful in guiding individualized treatments and surveillance.

The convenient Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor.

A fast and green protocol for the Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor was developed. In contrast with existing methods, this method is simple (35 min), uses mild reaction conditions (45 °C) and is environmentally friendly. This enzymatic Michael addition performed in continuous flow microreactors is an innovation that may open up the use of enzymatic microreactors in imidazole analogue biotransformations.

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma.

BACKGROUND: We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. METHODS: Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. RESULTS: We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). CONCLUSIONS: Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Deep-Blue and Hybrid-White Organic Light Emitting Diodes Based on a Twisting Carbazole-Benzofuro[2,3-b]Pyrazine Fluorescent Emitter.

A novel deep-blue fluorescent emitter was designed and synthesized. The external quantum efficiency (ηEQE) of the blue-emitting, doped, organic light-emitting diode (OLED) was as high as 4.34%. The device also exhibited an excellent color purity with Commission Internationale de l'Eclairage (CIE) coordinates of x = 0.15 and y = 0.05. In addition, the triplet energy had a value of 2.7 eV, which is rare for an emitter with deep-blue emission, which makes it a preferred choice for high-performance white OLEDs. By optimizing the device architectures, the color of hybrid-white OLEDs could be tunable from warm white to cool white using the aforementioned material as a bifunctional material. That is, the ηEQE of the hybrid warm-white OLED is 20.1% with a CIE x and y of 0.46 and 0.48 and the ηEQE of the hybrid cool-white OLED is 9% with a CIE x and y of 0.34 and 0.33.

The Control of Conjugation Lengths and Steric Hindrance to Modulate Aggregation-Induced Emission with High Electroluminescence Properties and Interesting Optical Properties.

A series of novel AIE-active (aggregation-induced emission) molecules, named SAF-2-TriPE, SAF-3-TriPE, and SAF-4-TriPE, were designed and synthesized through facile reaction procedures. We found that incorporation of the spiro-acridine-fluorene (SAF) group, which is famous for its excellent hole-transporting ability and rigid structure, at different substitution positions on the phenyl ring affected the conjugation lengths of these compounds. Consequently, we have obtained molecules with different emission colors and properties without sacrificing good EL (electroluminescence) characteristics. Accordingly, a device that was based on compound SAF-2-TriPE displayed superior EL characteristics: it emitted green light with ηc, max =10.5 cd A(-1) and ηext, max =4.22 %, whereas a device that was based on compound SAF-3-TriPE emitted blue-green light with ηc, max =3.9 cd A(-1) and ηext, max = 1.71 %. These compounds also displayed different AIE performances: when the fraction of water in the THF solutions of these compounds was increased, we observed a significant improvement in the ΦF of compounds SAF-2-TriPE and SAF-3-TriPE; in contrast, compound SAF-4-TriPE showed an abnormal phenomenon, in that it emitted a strong fluorescence in both pure THF solution and in the aggregated state without a significant change in ΦF . Overall, this systematic study confirmed a relationship between the regioisomerism of the luminophore structure and its AIE activity and the resulting electroluminescent performance in non-doped devices.

pH-regulated surface properties and pH-reversible micelle transition of a zwitterionic gemini surfactant in aqueous solution.

A zwitterionic gemini surfactant, called 2,2'-(1,4-phenylenebis(oxy))bis(N,N-dimethyl)-N-carboxyethyl-N-(alkylamide propyl) ammonium chloride (C14-B-C14), was synthesized successfully. The surfactant molecule exhibits various states at different pH values due to the two pH-sensitive carboxylate groups in the molecule. The surface activity and aggregate behaviors of C14-B-C14 in the aqueous solution were investigated under different pH conditions. The surface activities of the surfactant decrease with the increase in pH due to higher hydrophilic properties under basic conditions. The aggregate behaviours were also studied in acidic, near neutral and alkaline solutions, respectively. When the pH values of the solutions increased from acidic conditions to near neutral conditions (6.80), the samples immediately transformed from water-like solutions to viscoelastic fluids and remained gel-like under basic conditions. The changes in the appearance of the solution were due to the transition of the micelle structure from spherical to worm-like. Furthermore, this transition was reversible and repeated for at least 4 cycles. Finally, a reasonable mechanism of the appearance and transition of micelles was proposed based on the molecular states, viscoelastic properties and micelle structures.

pH-Regulated surface property and pH-reversible micelle transition of a tertiary amine-based gemini surfactant in aqueous solution.

A series of tertiary amide-based gemini surfactants, 2,2'-(1,4-phenylenebis(oxy))bis(N-(3-(dimethylamino)propyl)alkylamide), abbreviated as Cm-A-Cm (m = 8; 10; 12; 14), were synthesized. The surface property and aggregation behaviors of the Cm-A-Cm aqueous solutions were studied in detail. The Cm-A-Cm exhibited high and pH-regulated surface activity at the air/water interface; i.e., the critical micelle concentration was 5.6 × 10(-6) mol L(-1) at pH = 2.50 when m = 14 and was further regulated to 1.8 × 10(-6) mol L(-1) by altering the pH to 6.50. When the pH was tuned from 2.0 to 12.0, the appearance of the C12-A-C12 aqueous solution (35 mM) underwent 5 states: transparent water-like solution, viscous fluid, gel-like fluid, turbid liquid and dispersion system with white precipitate. The results of rheology, cryogenic transmission electron microscopy, and dynamic light scattering characterization revealed that the transition from water-like to viscous or gel-like liquid was actually due to aggregate microstructure transition from spherical to worm-like micelles. This transition was completely reversible between pH = 2.50 and 6.81, tuned by adding HCl and NaOH solutions for at least 4 cycles. Similar micellar transitions regulated by pH were also found for m = 8 and 10, whereas only worm-like micelles were formed for m = 14 at both acidic and nearly neutral conditions. Finally, a reasonable mechanism of aggregate behavior transition was proposed from the viewpoint of the molecular states, molecular structures, and the intra- and inter-molecular interactions.

Ultrafast removal of toxic Cr(VI) by the marine bacterium Vibrio natriegens.

The fastest-growing microbe Vibrio natriegens is an excellent platform for bioproduction processes. Until now, this marine bacterium has not been examined for bioremediation applications, where the production of substantial amounts of biomass would be beneficial. V. natriegens can perform extracellular electron transfer (EET) to Fe(III) via a single porin-cytochrome circuit conserved in Vibrionaceae. Electroactive microbes capable of EET to Fe(III) usually also reduce toxic metals such as carcinogenic Cr(VI), which is converted to Cr(III), thus decreasing its toxicity and mobility. Here, the performance of V. natriegens was explored for the bioremediation of Cr(VI). At a density of 100 mg/mL, V. natriegens removed 5-20 mg/L Cr(VI) within 30 s and 100 mg/L Cr(VI) within 10 min. In comparison, the model bacterium Escherichia coli grown to a comparable cell density removed Cr(VI) 36 times slower. To eliminate Cr(VI), V. natriegens had to be metabolically active, and functional outer-membrane c-type cytochromes were required. At the end of the Cr(VI) removal process, V. natriegens had reduced all of it into Cr(III) while adsorbing more than half of the metallic ions. These results demonstrate that V. natriegens, with its fast metabolism, is a viable option for the rapid treatment of aqueous pollution with Cr.

Revealing the active ingredients and mechanism of P. sibiricumm in non-small-cell lung cancer based on UPLC-Q-TOF-MS/MS, network pharmacology, and molecular docking.

The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of "components-targets-pathways" was established using Cytoscape 3.8.2 and assessed with the "network analyzer" plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(ß-d-glucopyranosyl)-furost-5-en3ß,22α,26-triol3-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.

DEB-TACE versus cTACE for unresectable HCC with B1-type bile duct invasion after successful biliary drainage: A propensity score matching analysis.

BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first-order branch of the bile ducts (B1-type bile duct invasion; B1-BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB-TACE with cTACE in this patient population. MATERIALS AND METHODS: Using data from five tertiary medical centers (January 2017-December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1-BDI who underwent DEB-TACE or cTACE after successful biliary drainage. X-tile software calculated the pre-TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. RESULTS: The study included 108 patients with unresectable HCC (B1-BDI) who underwent DEB-TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB-TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB-TACE group exhibited fewer post-procedural increments in the mean albumin-bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p < 0.05). The pre-TACE TBil cutoff value was 99 µmol/L; patients with higher values (>99 µmol/L) had poorer OS in both groups (p < 0.05). CONCLUSION: DEB-TACE is safe and effective after successful biliary drainage in unresectable HCC with B1-BDI, potentially better than cTACE in terms of liver toxicity, TTP, and ORR. Lowering TBil below 99 µmol/L through successful drainage may create ideal conditions for sequential TACE.

[Chemical Speciation, Influencing Factors, and Regression Model of Heavy Metals in Farmland of Typical Carbonate Area with High Geological Background, Southwest China].

The speciation of heavy metals in soil is an important factor determining their bioavailability and toxicity, and it is crucial for the scientific assessment of ecological risks posed by heavy metals in soils of typical carbonate areas with high geological background in southwest China. In order to investigate the distribution of speciation of heavy metals in soils of carbonate rock with high geological background, we selected a typical carbonate rock distribution area in Guizhou Province and used the second national soil survey plots as sampling units. A total of 309 topsoil samples were collected from farmland. The improved Tessier seven-step sequential extraction method was used to analyze the seven chemical forms of heavy metals:water-soluble (F1); exchangeable (F2); carbonate-bound (F3); weakly organic-bound (F4); iron-manganese oxide-bound (F5); strongly organic-bound (F6); and residual (F7) forms of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). The study found that the residual forms of heavy metals As, Cu, Hg, Ni, Pb, and Zn in the soil accounted for more than 50%, the effective components (F1-F3) accounted for less than 5%, and the potential biological effective components (F4-F6) were less than 45%, indicating low reactivity and low ecological risk. The effective and potentially bioavailable components of Cd accounted for 55.49% and 29.37%, respectively, which were much higher than those of other heavy metals. The ecological risk based on the speciation of heavy metals in the soil was much lower than that based on the total content of heavy metals. The stepwise regression equations could effectively establish the relationship between the bioavailable and potentially bioavailable fractions of Cd, Cu, and Pb and their influencing factors. Total heavy metal contents and pH value were important factors influencing the speciation of heavy metals in soils of carbonate rock with high geological background areas. The enrichment of heavy metal elements in the residual fraction was influenced by long-term zinc smelting activities and the weathering of carbonate rocks into soil. Soil organic matter (OM) and oxide content had a relatively small influence on the speciation of heavy metals in the soil.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.