Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance.

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant (P < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group (P < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group (P < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.

Real-Time Tunable Dynamic Range for Calibration-Free Biomolecular Measurements with a Temperature-Modulated Electrochemical Aptamer-Based Sensor in an Unprocessed Actual Sample.

The sensing technologies for monitoring molecular analytes in biological fluids with high frequency and in real time could enable a broad range of applications in personalized healthcare and clinical diagnosis. However, due to the limited dynamic range (less than 81-fold), real-time analysis of biomolecular concentration varying over multiple orders of magnitude is a severe challenge faced by this class of analytical platforms. For the first time, we describe here that temperature-modulated electrochemical aptamer-based sensors with a dynamically adjustable calibration-free detection window could enable continuous, real-time, and accurate response for the several-hundredfold target concentration changes in unprocessed actual samples. Specifically, we could regulate the electrode surface temperature of sensors to obtain the corresponding dynamic range because of the temperature-dependent affinity variations. This temperature modulation method relies on an alternate hot and cold electrode reported by our group, whose surface could actively be heated and cooled without the need for altering ambient temperature, thus likewise applying for the flowing system. We then performed dual-frequency calibration-free measurements at different interface temperatures, thus achieving an extended detection window from 25 to 2500 µM for procaine in undiluted urine, 1-500 µM for adenosine triphosphate, and 5-2000 µM for adenosine in undiluted serum. The resulting sensor architecture could drastically expand the real-time response range accessible to these continuous, reagent-less biosensors.

Research on a Defecation Pre-Warning Algorithm for the Disabled Elderly Based on a Semi-Supervised Generative Adversarial Network.

The elderly population in China is continuously increasing, and the disabled account for a large proportion of the elderly population. An effective solution is urgently needed for incontinence among disabled elderly people. Compared with disposable adult diapers, artificial sphincter implantation and medication for incontinence, the defecation pre-warning method is more flexible and convenient. However, due to the complex human physiology and individual differences, its development is limited. Based on the aging trend of the population and clinical needs, this paper proposes a bowel sound acquisition system and a defecation pre-warning method and system based on a semi-supervised generative adversarial network. A network model was established to predict defecation using bowel sounds. The experimental results show that the proposed method can effectively classify bowel sounds with or without defecation tendency, and the accuracy reached 94.4%.

Spectrum of psychiatric adverse reactions to cyclin-dependent kinases 4/6 inhibitors: A pharmacovigilance analysis of the FDA adverse event reporting system.

BACKGROUND: The emergence of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) represented a major breakthrough in the treatment of breast cancer over the past decade. In both clinical trials and real-world settings, it was observed that patients using CDK4/6i might experience psychiatric adverse events (PAEs). Herein, we conducted a pharmacovigilance study to comprehensively assess the correlation between CDK4/6i and PAEs. METHOD: We obtained individual case safety reports submitted to the FDA Adverse Events Reporting System (FAERS) during the period from January 2015 to December 2023. In disproportionality analysis, the reporting odds ratio (ROR) and information component (IC) values were calculated for each adverse event-drug combination. Univariate logistic regression analysis was utilized to explore factors associated with PAEs following CDK4/6i treatment. RESULTS: A total of 95,591 reports related to CDK4/6i were identified, with 6.72% reporting PAEs, and this proportion exhibited an annual upward trend. Based on the ROR and IC values, 17 categories of PAEs were defined as CDK4/6i-related PAEs. Among these PAEs, insomnia, stress, eating disorder, depressed mood, and sleep disorder were very common, each accounting for over 10% of CDK4/6i reports. Ribociclib showed the highest risk signal of CDK4/6i-related PAEs (ROR = 1.89[1.75-2.04], IC025 = 0.79), followed by palbociclib (ROR = 1.47[1.41-1.53], IC025 = 0.49), while abemaciclib did not exhibit a significant signal (ROR = 0.52[0.44-0.62], IC025 = -1.13). Female sex, younger age and weight exceeding 80 kg were significant risk factors for the incidence of CDK4/6i-related PAEs. CONCLUSIONS: Using data from a real-world, large-scale spontaneous reporting system for adverse drug reactions, our study delineated the spectrum of PAEs to CDK4/6i. This potentially offered valuable insights for healthcare professionals to manage the risk of PAEs in patients receiving CDK4/6i treatment, particularly those with psychiatric disorders.

Clinical significance of adjuvant therapy after radical surgery for primary osteosarcoma of the jaws.

BACKGROUND: Osteosarcoma of the jaw is one of the rare malignancies and the role of postoperative adjuvant therapy is unclear. This study explored the efficacy of adjuvant therapy after radical surgery for primary osteosarcoma of the jaw. METHODS: The data were retrospectively analyzed from May 2012 to June 2021. The recurrence rate, disease-free survival (DFS) and 5­year overall survival (OS) rate were calculated by Kaplan-Meier method. Intergroup rates were examined by chi-square test. RESULTS: 125 post-radical surgery patients were included. The median follow-up time was 66 months. Forty five cases suffered recurrence. The recurrence rate was 36.0%, and the 5­year OS rate was 68.8%. In the adjuvant treatment group, twenty eight of 99 patients experienced disease progression. In the surgical treatment alone group, seventeen of 26 patients experienced disease progression. The recurrence rates in the two groups were 28.3 and 65.4%, respectively (χ2 = 12.303, p < 0.001). The 5­year OS rate was 75.8 and 42.3%, respectively (χ2 = 10.734, p = 0.001). The median DFS of the relapse patients was 15.1 months (95% CI:13.00-17.20 months), and the 5­year OS rate was 40.0%. Among them, 28 patients received adjuvant therapy while 17 received surgical treatment alone. The median DFS was 15.7 and 11.5 months, respectively, p = 0.024. The median OS was 69.6 months (95% CI 55.69 ~ 83.51 months) and 62.4 months (95% CI 49.06 ~ 75.74 months), respectively(p = 0.034). CONCLUSION: Adjuvant therapy is one of the effective measures to reduce the relapse rate and improve OS after radical surgery for primary osteosarcoma of the jaw.

FOXP3 expression in esophageal squamous cell carcinoma : Implications for cetuximab sensitivity and therapeutic strategies.

OBJECTIVE: Investigating the impact of FOXP3 (transcription factor forkhead box P3) expression on the biological behavior of esophageal squamous cell carcinoma (ESCC) and its influence on the sensitivity of ESCC cells towards cetuximab-targeted (an EGFR monoclonal antibody inhibitor) therapy. METHODS: A specifically designed recombinant FOXP3 shRNA plasmid was synthesized to target the human FOXP3 gene, and the plasmid was transfected into TE12 cells using a liposome method. Multiple assays were conducted to evaluate the effect of FOXP3 expression on ESCC cells and their response to cetuximab treatment. Proliferation activity and cetuximab sensitivity of ESCC cells were measured using the CCK­8 assay. The invasion ability of cells was assessed using an in vitro invasion assay. Furthermore, the efficacy of cetuximab in treating ESCC was analyzed using a tumorigenesis assay in nude mice. RESULTS: Silencing the FOXP3 gene in the TE12 cell line (shFOXP3 group) resulted in a significant reduction in FOXP3 mRNA and protein expression (p = 0.013). The shFOXP3 group exhibited slowed cell growth (p = 0.035), decreased invasion rate (p = 0.031), and increased sensitivity to cetuximab treatment (p = 0.039) compared to the control group (shNC group). In the in vivo tumorigenesis assay, the shFOXP3 group demonstrated a significant reduction in tumor volume and lung metastasis rate following cetuximab treatment (p = 0.028 and 0.007, respectively). CONCLUSION: High FOXP3 expression promotes the proliferation and migration of ESCC cells, while negatively affecting their sensitivity to cetuximab-targeted therapy. Consequently, targeting FOXP3 shows potential therapeutic implications for enhancing the effectiveness of cetuximab treatment in ESCC patients.

Effect of Different Timing of Local Brain Radiotherapy on Survival of EGFR-Mutated NSCLC Patients with Limited Brain Metastases.

(1) Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been the first line therapy for EGFR-mutant lung adenocarcinoma (LAC) patients with brain metastases (BMs). However, the role and the optimal time of brain radiotherapy remains controversial. We aimed to investigate the role of upfront brain stereotactic radiotherapy (SRS) and the impact of deferral radiotherapy on patients' clinical outcomes. (2) Methods: We retrospectively studied 53 EGFR-mutant LAC patients with limited synchronous BMs between 2014 and 2020 at our institute. The limited BMs was defined with one to four BM lesions, with a maximal size of ≤4 cm. Patients were categorized into two groups: upfront brain SRS (upfront RT) and upfront TKIs. The intracranial progression-free survival (iPFS), progression-free survival (PFS), and overall survival (OS) between groups were analyzed. (3) Results: The median iPFS (21.0 vs. 12.0 months, p = 0.002) and PFS (20.0 vs. 11.0 months, p = 0.004) of the upfront RT group was longer than that of the upfront TKI group. There were no significant differences in median OS (30.0 vs. 26.0 months, p = 0.552) between the two groups. The upfront RT group is less likely to suffer from intracranial progression of the original sites than that of upfront TKIs during the disease course (36.1% vs. 0.0%, p = 0.025). Multivariate analysis showed that the Karnofsky Performance Scale and the presence of synchronous meningeal metastases were associated with overall survival. (4) Conclusions: Compared with upfront TKI, the combination of upfront SRS with TKIs can improve the iPFS and PFS in EGFR-mutant LAC with synchronous BMs. The addition of upfront brain SRS was useful for the original intracranial metastatic lesions.

Multi-cohort validation study of a four-gene signature for risk stratification and treatment response prediction in hepatocellular carcinoma.

BACKGROUND: The intricate molecular landscape of hepatocellular carcinoma (HCC) presents a significant challenge to achieving precise risk stratification through clinical genetic testing. At present, there is a paucity of robust gene signatures that could assist clinicians in making clinical decisions for patients with HCC. METHODS: We obtained gene expression profiles of patients with HCC from 20 independent cohorts available in public databases. A gene signature was developed by employing two machine learning algorithms. In addition to validating the signature with high-throughput data in public cohorts, we external validated the signature in 64 HCC cases by RT-PCR method. We compared genomic, transcriptomic and proteomic features between different subgroups. We also compared our signature to 130 gene signatures that have already been published. RESULTS: We developed a novel four-gene signature, designated as HCC4, that demonstrates significant potential for the prediction of survival outcomes in more than 1300 patients with HCC. The HCC4 also has potential for predicting recurrence and tumor volume doubling time, assessing transcatheter arterial chemoembolization and immunotherapy responses, and non-invasive detection of HCC. The high HCC4 score group shows a higher frequency of mutations in genes TP53, RB1 and TSC1/2, as well as increased activity of cell-cycle, glycolysis and hypoxia signaling pathways, higher cancer stemness score, and lower lipid metabolism activity. In seven HCC cohorts, HCC4 exhibited a higher average C-index in predicting overall survival compared to the 130 signatures previously published. Drug screening indicated that patients with high HCC4 scores were more sensitive to agents targeting AURKA, TUBB, JMJD6 and KIFC1. CONCLUSIONS: Our findings demonstrated that HCC4 is a powerful tool for improving risk stratification and for identifying HCC patients who are most likely to benefit from TACE treatment, immunotherapy, and other experimental therapies.

Rapid nanomolar detection of methamphetamine in biofluids via a reagentless electrochemical aptamer-based biosensor.

The availability of sensing platforms able to rapidly measure abused drugs directly in biological fluids in a single step would allow performing drugged driving screening on the site. The achievement of this goal is extremely important for preventing and controlling drug abuse and crime incidence. Motived by this, we constructed a simple, cost-effective and reagentless electrochemical aptamer-based (EAB) sensor with methamphetamine (MAMP) as the target molecule. This EAB sensor produced a nanomolar level of detection accuracy in unprocessed or minimally processed bio-samples. Specifically, circular dichroic spectrum was used to confirm that the truncated aptamer from the original sequence would undergo large binding-induced conformational changes. We then engineered the aptamer to work in the EAB platform and the resulting sensor enabled sensitive and specific detection of MAMP with the detection limit of 30 nM in undiluted serum, 50 nM in undiluted urine and 20 nM in 50% saliva. The sensor has good recovery rate, implying this method has good reliability and repeatability. The detection limit is far below the clinical detection threshold, it would be hopefully used for preliminary screening of drugged driving in real world.

Production of aromatic amines via catalytic co-pyrolysis of lignin and phenol-formaldehyde resins with ammonia over commercial HZSM-5 zeolites.

Aromatic amines could be produced from organic wastes via catalytic pyrolysis with ammonia that served not only as a carrier gas but also as a reactant. Aromatic amines of 14.2 C% with selectivity of 57.6% were obtained from phenol-formaldehyde resins via pyrolysis over commercial HZSM-5-3 zeolite (Si/Al ratio of 80) catalyst at 650 °C. Significant synergetic effects have been observed when lignin was added, which improved aromatic amines yield by 32.2% to 11.8 C% at the mixing weight ratio of lignin to PF resins of 1:1. HZSM-5-3 was slightly deactivated after 3 cycles with acid sites loss. Catalytic co-pyrolysis of plastics and biomass wastes is a fast and effective method to produce aromatic amines.

Monitoring colorless electroactive chemicals in complex background based on electrochemical difference absorption spectroscopy with twin flow cells.

Conventional UV/Vis absorption spectroscopy is an economical and user-friendly technique for online monitoring, however, by which some electroactive chemicals are hardly determined in the presence of fluctuating background due to the formation of colored chemicals. Here, we propose an electrochemical difference absorption spectroscopy (EDAS) to accurately quantify colorless chemicals based on visible color change via electrolysis with strong variation in the background. EDAS is realized by twin spectroelectrochemical flow cells system, replacing the two cuvette cells of a dual beam spectrophotometer. Each cell consists of a three-electrode system, quartz windows and a thin flow channel. Flowing of analyte from one cell (reference cell) to the other (sample cell) can eliminate the influence of colored interferents even while their concentrations are changing. When different potentials are applied on the sample and reference cells respectively, electrolysis occurs and colored products flowing through quartz windows can absorb the incident light, resulting in difference absorption spectra induced from potential difference. We find that steady-state difference absorbance (ΔA) at characteristic wavelength is linearly changed with sample concentrations. EDAS is firstly verified by Fe(CN)64- at different potentials and flow rates, in good agreements with a simplified theory that describes linear relationship between ΔA and analyte concentration. Then EDAS is used to determine Cu(I) in Cu(I)-Cu(II) mixed solutions and tetramethylbenzidine in its partially oxidized solutions to illustrate the powerful ability to detect colorless chemicals with varied background, implying its promising potential applications in the chemical industry.