Association Between Family History in Patients with Primary Gout and Left Ventricular Diastolic Function: A Cross-Sectional Study.

Objective: This study aimed to employ echocardiography for measuring the markers of left ventricular (LV) diastolic function to investigate the effects of family history of gout on the LV diastolic function in patients with primary gout. Methods: Two hundred and eighty-four patients with primary gout who visited the Department of Rheumatology and Immunology of the First Affiliated Hospital of Chengdu Medical College from September 2020 to July 2022 were selected and their family history of gout, general information, and laboratory markers were recorded. Parameters of LV diastolic function were measured via echocardiography. The correlation between family history and LV diastolic function markers was analyzed using univariate and multivariate regression and the receiver operating characteristic (ROC) curve analyses. Results: LV diastolic function parameters, peak early mitral diastolic velocity (E)/peak late mitral diastolic velocity (A), and early septal mitral annulus diastolic motion velocity (Sepe'), early lateral mitral annulus diastolic motion velocity (Late') and their mean (e'), were significantly lower in patients with familial primary gout, while left atrial volume index (LAVI) and E/e' were markedly elevated in patients with sporadic primary gout. In patients with family history, the proportion of grade ≥2 LV diastolic insufficiency was distinctly higher than that in patients without family history (41.6% vs 12.3%). Even after adjusting for confounding variables, LAVI, E/A, Sepe', Late', e', E/e' were obviously associated with family history of gout. The area under ROC of family history combined with SUA level for identifying grade ≥2 LV diastolic insufficiency in patients with primary gout was 0.872 (P<0.05). Conclusion: Family history of gout was closely related to echocardiographic LV diastolic function parameters in patients with gout, what is more, family history of gout combined with SUA level was found to be a valuable indicator for discriminating grade ≥2 LV diastolic insufficiency in patients with primary gout.

Safety and efficacy evaluation of personalized exercise prescription during chemotherapy for lung cancer patients.

BACKGROUND: To explore the safety and effectiveness of personalized exercise intervention during chemotherapy for lung cancer patients who were relatively weak and with compromised cardiopulmonary function. METHODS: Thirty-eight lung cancer patients treated with chemotherapy at Peking University Third Hospital were enrolled in this prospective study. The exercise group (N = 21) received individualized exercise guidance based on personal test results and exercised regularly, while the control group (N = 17) only received exercise education and planed exercise methods according to their own preferences. Both groups underwent three fitness tests and clinical indicator assessments at 0, 6, and 12 weeks after starting the exercise, and the differences in trends of various indicators between the two groups were compared. RESULTS: No exercise-related adverse events occurred during the 12-week exercise period. After 12 weeks of exercise training, in terms of fitness, the exercise group showed significant improvements in 6-min walk test (6MWT) (p < 0.001), peak oxygen consumption (VO2peak) (p = 0.005), muscle content (p < 0.001), muscle percentage (p < 0.001), and grip strength (p = 0.008) compared to the control group. In terms of clinical indicators, the exercise group showed significant improvements in vital capacity (p = 0.018), D-dimer (p = 0.031), and C-reactive protein (CRP) (p = 0.01), uric acid (p = 0.003), triglycerides (p < 0.001), functional average score (p < 0.001), and main symptom average score (p = 0.004) compared to the control group in trends over time. CONCLUSION: Rehabilitation exercises using individualized exercise prescriptions tailored by exercise prescription specialists during chemotherapy are safe for lung cancer patients. Adhering to exercise can achieve comprehensive improvements in physical fitness and quality of life at 12 weeks.

Efficient purification and high-quality regeneration of graphite from spent lithium-ion batteries by surfactant-assisted methanesulfonic acid.

With the vigorous development of the new energy industry, the use of lithium-ion batteries (LIBs) is growing exponentially, and the recycling of spent LIBs has gradually become a research hotspot. Currently, recycling both cathode and anode materials of LIBs is important to environmental protection and resource recycling. This research reportsa method ofefficient purification and high-quality regeneration of graphite from spent LIBs by surfactant-assisted methanesulfonic acid (MSA). Under the optimal conditions (0.006 mol/L sodium dodecyl sulfonate, 0.25 mol/L MSA, 10 vol% hydrogen peroxide, liquid-solid ratio of 30:1 mL/g, 60 °C, 1.5 h), the purity of the regenerated graphite was 99.7 %, and the recovery efficiency was 98.0 %. The regenerated graphite showed the characteristics of small interplanar spacing, high degree of graphitization, a small number of surface defects, and excellent pore structure, which was closer to commercial graphite. Furthermore, the regenerated graphite electrode exhibited superior rate performance and cycling stability with a high specific capacity of 397.03 mAh/g after 50 cycles at 0.1C and a charge-discharge efficiency of 99.33 %. The recovery of anode graphite beneficial for resource utilization, environmental protection, and cost control throughout the entire production chain.

Closed-loop recovery of molybdenum and value-added reuse of tungsten from alloy waste in additive manufacturing.

As metal additive manufacturing (MAM) technology is booming in the aerospace sector, alternatives to the traditional production methods of metals such as mining, processing, and refining with severe emissions are urgently needed. This study proposed a closed-loop route for efficient recovery of molybdenum (Mo) and value-added reuse of tungsten (W) from Cr-Co-Ni-Mo-W alloy waste in MAM. The results showed that the leaching efficiency of Mo and W reached 99.3% and 99.9%, respectively, using the dual chemical-physical means of mixed-alkali roasting and leaching by microwave heating, while the discharge of waste liquor containing Cr6+ was reduced. Leaching kinetic studies revealed that the metal leaching process was controlled by chemical reaction mechanism. Moreover, the 10%N1923 (primary amine)-5%TRPO (tri-alkyl phosphine oxide)-kerosene extraction system exhibited a synergistic extraction effect on Mo and W. After purification, Mo was recovered as Mo powder for MAM. Simultaneously, the recovered product of W, MnWO4, was applied as a photocatalytic material with excellent degradation of methylene blue dye. Ultimately, the proposed method obtained recovery efficiencies of 98.4% and 99.3% for Mo and W, respectively, achieving efficient and environmentally-friendly reuse of these key metals.

A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins.

Development of effective therapies against SARS-CoV-2 infections relies on mechanistic knowledge of virus-host interface. Abundant physical interactions between viral and host proteins have been identified, but few have been functionally characterized. Harnessing the power of fly genetics, we develop a comprehensive Drosophila COVID-19 resource (DCR) consisting of publicly available strains for conditional tissue-specific expression of all SARS-CoV-2 encoded proteins, UAS-human cDNA transgenic lines encoding established host-viral interacting factors, and GAL4 insertion lines disrupting fly homologs of SARS-CoV-2 human interacting proteins. We demonstrate the utility of the DCR to functionally assess SARS-CoV-2 genes and candidate human binding partners. We show that NSP8 engages in strong genetic interactions with several human candidates, most prominently with the ATE1 arginyltransferase to induce actin arginylation and cytoskeletal disorganization, and that two ATE1 inhibitors can reverse NSP8 phenotypes. The DCR enables parallel global-scale functional analysis of SARS-CoV-2 components in a prime genetic model system.

Preparation and Performance of Regenerated Al2O3-Coated Cathode Material LiNi0.8Co0.15Al0.05O2 from Spent Power Lithium-Ion Batteries.

In this study, LiNi0.8Co0.15Al0.05O2@x%Al2O3-coated cathode materials were regeneratively compounded by the solid-phase sintering method, and their structural characterization and electrochemical performance were systematically analyzed. The regenerated ternary cathode material precursor synthesized by the co-precipitation method was roasted with lithium carbonate at a molar ratio of 1:1.1, and then completely mixed with different contents of aluminum hydroxide. The combined materials were then sintered at 800 °C for 15 h to obtain the regenerated coated cathode material, LiNi0.8Co0.15Al0.05O2@x%Al2O3. The thermogravimetry analysis, phase composition, morphological characteristics, and other tests show that when the added content of aluminum hydroxide is 3%, the regenerated cathode material, LiNi0.8Co0.15Al0.05O2@1.5%Al2O3, exhibits the highest-order layered structure with Al2O3 coating. This material can better inhibit the production of Ni2+, and improve material structure and electrochemical properties. The first charge-discharge efficiency of the battery assembled with this regenerated cathode material is 97.4%, a 50-cycle capacity retention is 93.4%, and a 100-cycle capacity retention is 87.6%. The first charge-discharge efficiency is far better than that of the uncoated regenerated battery.

PD-L1 Biomolecules Associated with Clinical Features in Non-Melanoma Skin Cancer.

Background: Increasing evidence has indicated that several B7 family members play critical roles in the progress of many cancers. However, the clinical significance of the B7 family in cutaneous squamous cell carcinoma (cSCC) is still elusive. The purpose of this study is to investigate the potential role of B7-H1 biomolecules (PD-L1) in regulating the tumorigenesis and progression of cSCC, the most common non-melanoma skin cancer. Methods: We collected transcriptome data of cSCC patients from TCGA databases (n = 496) and subjected the transcription data to bioinformatical analysis. Differential expression of B7-H1 genes with a grade-dependent pattern was identified. We collected paraffin sections of skin squamous carcinoma and analyzed by immunohistochemical staining. We further examined the PD-L1 levels of CD14+ cells in peripheral blood of each cSCC patient and normal subjects by flow cytometry. Results: It was found that higher expression of PD-L1 was associated with poor prognosis of cSCC patients and shorter overall survival. These observations were further verified in the clinical paraffin sections and in peripheral blood T cells. Conclusion: Our study reveals that PD-L1 is a potential prognostic marker in clinical prognosis for cSCC patients and could be valuable for cSCC treatment.

Diagnostic value and safety of ultrathin bronchoscope and endobronchial ultrasonography with a guide sheath combined with rapid on-site evaluation system for peripheral pulmonary infectious diseases.

BACKGROUND: The aim of this study was to investigate the diagnostic value and safety of ultrathin bronchoscope and endobronchial ultrasonography with a guide sheath (EBUS-GS) combined with rapid on-site evaluation (ROSE) system for peripheral pulmonary infectious diseases. METHODS: The clinical data of 196 patients visiting our hospital, who had peripheral pulmonary lesions (PPLs) indicated by spiral computed tomography (CT) of the chest and were finally diagnosed as infectious PPLs, were retrospectively collected. Then the patients were divided into ultrathin bronchoscope + ROSE group, EBUS-GS + ROSE group and ultrathin bronchoscope + EBUS-GS + ROSE group based on different diagnostic techniques. Moreover, the general conditions, diagnostic results and specific operation parameters of the patients were recorded, and the diagnostic rate, sensitivity and complications were compared. RESULTS: In ultrathin bronchoscope + EBUS-GS + ROSE group, the time of localizing lesions and operation time were the shortest, and the grade of bronchi reached by the bronchoscope was the highest. The differences were significant between any two groups (P<0.05). Patients with bacterial pneumonia, and patients with pulmonary tuberculosis and nontuberculous mycobacterial disease, ultrathin bronchoscope + EBUS-GS + ROSE group exhibited the highest definite diagnosis rate of bronchoscope and diagnostic sensitivity of ROSE system, with significant differences from those of the other two groups (P<0.05). The incidence rates of complications were low in all groups, and there were no significant differences between any two groups (P>0.05). CONCLUSIONS: Ultrathin bronchoscope and EBUS-GS combined with ROSE system can prominently decrease the time of localizing lesions and operation time, remarkably improve the diagnostic accuracy and sensitivity and result in fewer complications.

Safety and effectiveness of apatinib in elderly patients with metastatic gastric cancer: a sub-analysis from the large-scale, prospective observational study of apatinib for gastric cancer treatment in a real-world clinical setting (AHEAD-G202).

Background: Apatinib was shown to improve the survival of Chinese patients with refractory metastatic gastric cancer (mGC). As an orally administered drug, it has been widely used in elderly patients because the dosing schedule can be adjusted flexibly. However, data on the efficacy and safety of apatinib in elderly patients is scarce. The aim of this study was to evaluate the toxicity and effectiveness of apatinib for elderly patients with mGC in a real-world setting. Methods: Data from the sub-population of patients who were ≥65 years enrolled in the AHEAD-G202 trial were analyzed. Patients with mGC were prospectively registered and initially received ≤850 mg oral apatinib daily combined or not combined with chemotherapy, at the investigator's discretion. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 117 patients were included. There were 51 (43.59%) patients in the low-dose (250 mg) group, 60 (51.28%) patients in the mid-dose (425 to 500 mg) group, and 6 (5.13%) patients in the high-dose (850 mg) group according to the initial daily doses. Hypertension (6.84%) was the only grade 3-4 adverse event (AE) with a prevalence of more than 5% and across the low-dose (11.76%), mid-dose (3.33%) and high-dose group (0%). The median OS and PFS were 7.13 months (95% CI: 5.04 to 9.22 months) and 4.27 months (95% CI: 3.24 to 5.29 months), respectively. The OS and PFS were similar among the 65-74 and ≥75 years groups (χ2=1.406, P=0.306; χ2=0.378, P=0.066, respectively). The OS and PFS were also comparable among the 3 dose groups. Conclusions: Elderly patients with mGC can tolerate and benefit from apatinib therapy. A lower initial daily dosing strategy may be a suitable choice for elderly patients in clinical practice.

Construction of Circadian Clock Signature for Tumor Microenvironment in Predicting Survival for Cutaneous Melanoma.

OBJECTIVE: We explored circadian clock-related genes (CCRG) to establish a risk model and identify associations with the tumor immune microenvironment in cutaneous melanoma (CM). METHODS: Circadian clock genes were downloaded from Circadian Gene Database. To explore CM-related circadian clock genes, we combined multivariate cox regression associated with least absolute shrinkage and selection operator (LASSO) regression in the Cancer Genome Atlas (TCGA) and validated it in the GSE65904 dataset. Time-dependent receiver operating characteristic curve (ROC) and Kaplan-Meier analysis were calculated to determine a CCRG risk score model. In addition, the overall survival nomograms of clinicopathological factors and circadian clock-related gene signatures. Additionally, we evaluated the connection between circadian clock-related genes with immune checkpoint inhibitors and immune cell infiltration. RESULTS: Two circadian clock-related signatures were established. The risk model included SEMA4D (p<0.001, HR: 0.709, 95% CI: 0.581 to 0.867) and SOD-2 (p=0.009, HR: 0.790, 95% CI: 0.663 to 0.944) in patients with TCGA melanoma. The risk model was based on two CCRGs enriched in base excision repair, glycosylphosphatidyl (GPI), and one carbon of the folate pathway. The overall survival was lower in the high-risk group. In addition, the circadian-clock signature may be able to evaluate the immunotherapy response. CONCLUSIONS: We developed and validated a circadian signature to characterize the clinical significance and tumor microenvironment of cutaneous melanoma, revealing that circadian rhythms may impact cutaneous melanoma.

Novel Styrene-Based Polyamine Sorbent for Efficient Selective Separation of Molybdenum.

Tungsten (W) and molybdenum (Mo) are important strategic resources but the two coexist in both primary ore and waste. Before a single metal product is obtained, it is often necessary to separate the two. In this work, we reported two new polyamine resins (D301@PA and D301@TA), which can be obtained by an assembled amine (primary amine or tertiary amine) and traditional D301 resin by the dipping method. Then, the sorption experiments with the amine resins were carried out, and the selectivity and sorption capacity of the two new polyamine resins for MoS4 2- have been significantly improved. Among them, D301@TA showed the highest sorption capacity of 414 mg·g-1 and a separation factor of 108. Finally, the sorption mechanism can be inferred through scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, and X-ray photoemission spectroscopy (XPS); the Cl- ions in the amine resin and the MoS4 2- ions were subjected to ion exchange. This work provides a green and efficient approach for separating tungsten and molybdenum.

An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination.

Previously, we described a large collection of Drosophila strains that each carry an artificial exon containing a T2AGAL4 cassette inserted in an intron of a target gene based on CRISPR-mediated homologous recombination. These alleles permit numerous applications and have proven to be very useful. Initially, the homologous recombination-based donor constructs had long homology arms (>500 bps) to promote precise integration of large constructs (>5 kb). Recently, we showed that in vivo linearization of the donor constructs enables insertion of large artificial exons in introns using short homology arms (100-200 bps). Shorter homology arms make it feasible to commercially synthesize homology donors and minimize the cloning steps for donor construct generation. Unfortunately, about 58% of Drosophila genes lack a suitable coding intron for integration of artificial exons in all of the annotated isoforms. Here, we report the development of new set of constructs that allow the replacement of the coding region of genes that lack suitable introns with a KozakGAL4 cassette, generating a knock-out/knock-in allele that expresses GAL4 similarly as the targeted gene. We also developed custom vector backbones to further facilitate and improve transgenesis. Synthesis of homology donor constructs in custom plasmid backbones that contain the target gene sgRNA obviates the need to inject a separate sgRNA plasmid and significantly increases the transgenesis efficiency. These upgrades will enable the targeting of nearly every fly gene, regardless of exon-intron structure, with a 70-80% success rate.

Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients.

OBJECTIVE: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients. METHODS: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan-Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration. RESULTS: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response. CONCLUSION: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.

Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: adjusting macrophage polarization through the activin receptor-follistatin system.

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

Vanadium Pentoxide Nanofibers/Carbon Nanotubes Hybrid Film for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) with the characteristics of low production costs and good safety have been regarded as ideal candidates for large-scale energy storage applications. However, the nonconductive and non-redox active polymer used as the binder in the traditional preparation of electrodes hinders the exposure of active sites and limits the diffusion of ions, compromising the energy density of the electrode in ZIBs. Herein, we fabricated vanadium pentoxide nanofibers/carbon nanotubes (V2O5/CNTs) hybrid films as binder-free cathodes for ZIBs. High ionic conductivity and electronic conductivity were enabled in the V2O5/CNTs film due to the porous structure of the film and the introduction of carbon nanotubes with high electronic conductivity. As a result, the batteries based on the V2O5/CNTs film exhibited a higher capacity of 390 mAh g-1 at 1 A g-1, as compared to batteries based on V2O5 (263 mAh g-1). Even at 5 A g-1, the battery based on the V2O5/CNTs film maintained a capacity of 250 mAh g-1 after 2000 cycles with a capacity retention of 94%. In addition, the V2O5/CNTs film electrode also showed a high energy/power density (e.g., 67 kW kg-1/267 Wh kg-1). The capacitance response and rapid diffusion coefficient of Zn2+ (~10-8 cm-2 s-1) can explain the excellent rate capability of V2O5/CNTs. The vanadium pentoxide nanofibers/carbon nanotubes hybrid film as binder-free cathodes showed a high capability and a stable cyclability, demonstrating that it is highly promising for large-scale energy storage applications.

Highly efficient sorption of molybdenum from tungstate solution with modified D301 resin.

The separation of molybdenum (Mo) from tungstate solution is a bottleneck problem in tungsten (W) metallurgy, and it hinders the development of high-purity tungsten materials. In this research, a modified D301 resin was used to adsorb and separate molybdenum from tungstate solution. The maximum sorption capacity (Q e) of modified D301 for MoS4 2- was found to be 428 mg g-1 and the separation coefficient (ß) was 108.9 when the contact time was 4 h and the reaction temperature was 25 °C and the pH value of the tungstate solution was 7.2. The sorption process conforms to Langmuir isotherm models and the quasi-second-order kinetic model. The sorption mechanism was also discussed, which was a single layered spontaneous sorption process. Theoretical calculations infer bonding behavior between the N atom on the resin and the S atom on the MoS4 2- molecule. The sorption energy is -7.67 eV, which indicated that the sorption process is stable chemical sorption. The desorption experiment showed that more than 90% molybdenum could be desorbed from the loaded resin when the concentration of sodium hydroxide solution was 5 w%. Finally, after three-stage sorption-desorption, almost all molybdenum in the solution was adsorbed, achieving better separation of tungsten and molybdenum.

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.

BACKGROUND: Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting. METHODS: From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR). RESULTS: Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median OS was 4.5 months (95%CI: 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%). CONCLUSION: Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer. TRIAL REGISTRATION: AHEAD-G202 (NCT02668380).

The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro.

AG490 is a selective inhibitor of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. The present study examined its effects on the abnormal behavior of human keloid fibroblasts (HKFs) and evaluated its potential use in the treatment of keloids. Human normal fibroblasts (HNFs) and HKFs were treated with increasing concentrations of AG490. The proliferation of HNFs and HKFs was inhibited by AG490 in both a time­ and concentration­dependent manner by increasing apoptosis and inducing G1 cell cycle arrest. The downregulation of cyclin D1 and connective tissue growth factor (CTGF) expression was associated with a decrease in STAT3 expression in response to AG490. The effects of AG490 on TGF­ß­stimulated fibroblasts, including HNFs, HKFs and hypertrophic scar fibroblasts (HSFs) were also evaluated. The TGF­ß1­stimulated excessive proliferation and CTGF production were markedly inhibited by the application of AG490 in the HNFs, HSFs and HKFs. In addition, the STAT3­specific decoy oligodeoxynucleotides (SODNs) were transfected into HKFs. The invasive ability of the SODN­transfected HKFs was determined and the expression of extracellular matrix components was quantified. Similarly, SODNs blocked the constitutive activation of STAT3. SODNs inhibited the invasion and progression of HKFs, possibly via the upregulation of the expression of tissue inhibitor of metalloproteinase­2 (TIMP­2), and the downregulation of the expression of matrix metalloproteinase­2 (MMP­2) and vascular endothelial growth factor (VEGF). On the whole, the findings of the present study demonstrate that STAT3­specific elimination, such as the application of AG490 and decoy ODNs, may serve as promising therapeutic strategies for the treatment of keloids.

Safety and effectiveness of apatinib in patients with previously treated metastatic gastric cancer: a sub-analysis from the real-world study of apatinib for gastric cancer treatment (AHEAD-G202).

Apatinib, a VEGFR2 receptor tyrosine kinase inhibitor, showed survival benefits in Asian patients with heavily pretreated advanced gastric cancer. However, the adverse event (AEs) profile of apatinib has limited its use. Dosing schedules are used to alleviate toxicities despite no supportive evidence. This study aimed to analyze the toxicity and effectiveness of apatinib alone, especially with different dosing strategies in advanced gastric cancer patients under a real-world setting. Data from the subpopulation of patients who failed ≥2 chemotherapy regimens enrolled in the AHEAD-G202 trial were analyzed. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Totally 120 patients were included into three groups by the initial daily doses: 43 (35.8%) patients in the low-dose (250 mg) group, 67 (55.8%) patients in the mid-dose (425 mg to 500 mg) group, and 10 (8.3%) patients in the high-dose (675 to 850 mg) group. Grade 3/4 treatment-emergent AEs were infrequent (<5%), with the most commonly reported grade 3/4 AEs being hand-foot syndrome (4.2%), hypertension (4.2%,), fatigue (4.2%), and difficulty in swallowing (4.2%) which gradually decreased among the high-, mid-, and low-dose groups. The median OS and PFS were 6.33 months (95% CI, 4.57-7.73) and 3.83 months (95% CI: 1.40-4.20), respectively and were comparable among the three doses groups. We found heavily pretreated advanced gastric cancer patients can tolerate and benefit from lower-doses of apatinib therapy. The lower initial daily dosing strategy represents an alternative approach for optimizing apatinib dosing in clinical practice.

An open label, multicenter, noninterventional study of apatinib in advanced gastric cancer patients (AHEAD-G202).

BACKGROUND: Apatinib has been proved to be effective and well tolerated among patients in phase II and III studies. Here, we evaluated the safety and effectiveness of apatinib in advanced gastric cancer patients in a real-world setting. METHODS: This study enrolled advanced gastric cancer patients who had progressed or relapsed despite systemic chemotherapy. The primary outcome was safety and the secondary outcomes included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 337 patients were included. In total, 62 (18.4%), 102 (30.3%), and 173 (51.3%) patients received first, second, and third or higher line apatinib therapy, respectively. Grade 3/4 treatment-emergent adverse events (AEs) were infrequent (<5%), with hypertension (6.8%) being the only grade 3/4 AE occurring in more than 5% of the patients and across the low-dose (250 mg, 7.3%), mid-dose (425-500 mg, 6.1%), and high-dose group (675-850 mg, 2/15, 13.3%). The median OS and PFS were 7.13 months (95% CI, 6.17-7.93) and 4.20 months (95% CI, 4.60-4.77), respectively, and were comparable among the low-, mid-, and high-dose groups. CONCLUSION: Lower daily doses of apatinib achieved comparable OS and PFS versus higher daily doses of apatinib while maintaining a more benign safety profile in advanced gastric cancer patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02668380.