Synthesis and biological evaluation of novel penindolone derivatives as potential antiproliferative agents against SCLC in vitro.

Small cell lung cancer (SCLC) keeps on the leading cause of cancer mortality world widely, while there is lack of efficient therapeutic drugs especially for the resistant ones. In this work, a compound named penindolone (PND) with new skeleton was found to show weak inhibitory effect (IC50 = 42.5 µM) on H69AR cells (SCLC, adriamycin-resistant) proliferation by screening our in-house compound library. With the aim of improving its low potency, a series of PND derivatives were synthesized and biologically evaluated by the Sulforhodamine B (SRB) assay. Among all tested derivatives, compound 5h possessed higher antiproliferation potency (IC50 = 1.6 µM). Furthermore, preliminary mechanism investigation revealed that 5h was able to induce apoptosis and arrest the cell cycle at G0/G1 phase. These findings suggest that this novel skeleton has expanded the anti-SCLC compound reservoir and provided a new drug lead.

Regulatory Peptide Encoded by the Primary Transcript of miR396a Influences Gene Expression and Root Development in Solanum lycopersicum.

MicroRNAs (miRNAs) are the processing products of primary miRNAs (pri-miRNAs) that regulate the expression of target genes. Recent studies have demonstrated that some pri-miRNAs can encode small peptides (miPEPs) that perform significant biological functions. The function of miPEPs in tomatoes, an important model horticultural crop, remains to be investigated. Here, we characterized the primary sequence of tomato miR396a using 5' RACE and confirmed the presence of miPEP396a in tomato by verifying the translational activity of the start codon. It primarily resides in the nucleus to exert its function and additionally regulates the expression of pri-miR396a, miR396a, and its target genes. Transcriptomic and metabolomic analyses showed that in vitro synthesis of miPEP396a significantly increased the expression of genes related to phenylpropanoid biosynthesis and hormones in tomato. Meanwhile, our in vitro application of miPEP396a in tomato significantly inhibited the elongation of tomato primary roots. In conclusion, our results indicate that miPEP396a regulates root growth in tomato by specifically promoting miR396a expression, provide insight into the function of miPEPs in tomato and potential applications.

Sidewall Corrugation-Modulated Phase-Apodized Silicon Grating Filter.

In this work, phase-apodized silicon grating filters with varying sidewall corrugation width and location were investigated, while the resonance wavelength, extinction ratio, and rejection bandwidth were tuned flexibly. The grating filters with a waveguide width of 500 nm and grating period of 400 nm were fabricated and characterized as a proof of concept. The resonance wavelength of the device can be shifted by 4.54 nm by varying the sidewall corrugation width from 150 to 250 nm. The corresponding rejection bandwidth can be changed from 1.19 to 2.03 nm by applying a sidewall corrugation location offset from 50 to 200 nm. The experimental performances coincide well with the simulation results. The presented sidewall corrugation-modulated apodized grating can be expected to have great application prospects for optical communications and semiconductor lasers.

DSOMF: A Dynamic Environment Simultaneous Localization and Mapping Technique Based on Machine Learning.

To address the challenges of reduced localization accuracy and incomplete map construction demonstrated using classical semantic simultaneous localization and mapping (SLAM) algorithms in dynamic environments, this study introduces a dynamic scene SLAM technique that builds upon direct sparse odometry (DSO) and incorporates instance segmentation and video completion algorithms. While prioritizing the algorithm's real-time performance, we leverage the rapid matching capabilities of Direct Sparse Odometry (DSO) to link identical dynamic objects in consecutive frames. This association is achieved through merging semantic and geometric data, thereby enhancing the matching accuracy during image tracking through the inclusion of semantic probability. Furthermore, we incorporate a loop closure module based on video inpainting algorithms into our mapping thread. This allows our algorithm to rely on the completed static background for loop closure detection, further enhancing the localization accuracy of our algorithm. The efficacy of this approach is validated using the TUM and KITTI public datasets and the unmanned platform experiment. Experimental results show that, in various dynamic scenes, our method achieves an improvement exceeding 85% in terms of localization accuracy compared with the DSO system.

A Survey on the Knowledge, Attitudes, Behaviors and Influencing Factors of Caregivers for Newborns With COVID-19 in Chongqing, China.

OBJECTIVE: This study aimed to investigate the healthcare knowledge, attitudes, and behaviors of primary caregivers of newborns with coronavirus disease 2019 (COVID-19) during the pandemic in Chongqing, China, and analyze the influencing factors. METHODS:  The study included primary caregivers of COVID-19 newborns hospitalized in our institution from December 2022 to January 2023. A questionnaire survey was initiated to assess the caregivers' health-care knowledge, attitudes, and behaviors for COVID-19 and the influencing factors. The data were analyzed statistically. RESULTS: A total of 195 caregivers were included, one for each infant with COVID-19. The questionnaire consisted of three dimensions. For the knowledge dimension, the top scoring items were wearing masks in public spaces (4.92 ± 0.087), strengthening hand hygiene (4.83 ± 0.164), and frequent ventilation in living environment (4.62 ± 0.331) in order; for the attitude dimension, the top three scoring items were wearing masks in public spaces (4.85 ± 0.353), strengthening hand washing and disinfection (4.72 ± 0.450), and regular ventilation (4.49 ± 0.501). For the behavior dimension, the top three were confidence in winning the challenge of the pandemic (4.71 ± 0.480), standardized wearing of masks in public spaces/confined spaces (4.68 ± 0.589), and high satisfaction with community epidemic prevention measures (4.67 ± 0.496). Among the influencing factors, fear of COVID-19 was the independent risk indicator for the caregivers' anxiety (OR = 38.085, 95% CI = 14.383-100.664) and fear of COVID-19 (OR = 8.170, 95%CI = 2.156-30.957) and fever (OR = 10.213, 95% CI = 1.972-52.892) were the independent risk indicators for depression. CONCLUSION:  The study shows a key link between caregiver knowledge, attitudes, behaviors, and neonatal COVID-19 infection, with a gap between knowledge, attitudes, and behaviors. Caregivers, especially those dealing with premature infants, worried about mother-to-child transmission and experienced multiple births, face significant psychological stress during this phase of the pandemic.

Recent Advances in the Modification and Improvement of Bioprosthetic Heart Valves.

Valvular heart disease (VHD) has become a burden and a growing public health problem in humans, causing significant morbidity and mortality worldwide. An increasing number of patients with severe VHD need to undergo heart valve replacement surgery, and artificial heart valves are in high demand. However, allogeneic valves from donors are lacking and cannot meet clinical practice needs. A mechanical heart valve can activate the coagulation pathway after contact with blood after implantation in the cardiovascular system, leading to thrombosis. Therefore, bioprosthetic heart valves (BHVs) are still a promising way to solve this problem. However, there are still challenges in the use of BHVs. For example, their longevity is still unsatisfactory due to the defects, such as thrombosis, structural valve degeneration, calcification, insufficient re-endothelialization, and the inflammatory response. Therefore, strategies and methods are needed to effectively improve the biocompatibility and longevity of BHVs. This review describes the recent research advances in BHVs and strategies to improve their biocompatibility and longevity.

Quality of life and decision regret in patients with late-hypothyroidism after radioiodine treatment for Graves' disease.

OBJECTIVE: Patients with Graves' disease often engage in shared decision-making to select an individualised treatment regimen from multiple options. Radioactive iodine (RAI) is one of the treatment choices for their condition, aims to improve quality of life and well-being. Likewise, dissatisfaction with treatment outcomes can result in decision regret. We employed validated questionnaires to assess the prospective quality of life, decision regret and relative factors involved in decision-making of patients with late hypothyroidism after RAI therapy. METHODS: A questionnaire survey was conducted among patients in hypothyroidism status for more than 1 year after RAI therapy. Disease-specific and generic QoL were assessed using the short form of thyroid-related patient-reported outcome (ThyPRO-39) questionnaire. Patient satisfaction regarding their decision to undergo RAI was assessed using the Decision Regret Scale (DRS) and patients were asked about the importance of relative factors in decision-making. RESULTS: Of 254 patients who responded to the survey, the mean age of patients was 45.3 years (range: 18-78 years) and the median time from RAI therapy to survey was 4 years (range: 1-30 years). Patients' median and mean DRS score were 34.4 and 38.8 (range: 0-100), respectively. A total of 100 (39.4%) patients express absent-to-mild regret (score: 0-25), 154 (60.6%) patients express moderate-to-severe regret (score: >25). The mean score of the absent-to-mild regret group were significantly higher than those of the moderate-to-severe regret group on most ThyPRO-39 scales. A statistically significant positive correlation was observed between DRS score and most ThyPRO-39 scale score. There was a significant positive association between higher DRS score and longer time intervals after RAI treatment, a brief duration of hyperthyroidism, and the significance of long-time outpatient follow-up. More decision regret was negatively associated Iodine-free diet, ineffectiveness of ATD, fear of surgery. CONCLUSION: Impairment of quality of life was positively correlated with decision regret in patients with late-hypothyroidism after radioiodine therapy. Patients with insufficient information support before decision-making are more likely to have higher decision regret after treatment. Our findings suggest that health providers should fully communicate with patients and provide information support in multiple dimensions during the shared-decision-making process.

Preparation, Characterization, and Properties of UV-Curable Coating Doped with Nano-SiO2.

In this study, a hydrophobic, wear-resistant ultraviolet (UV)-curable coating was investigated as an alternative to traditional coatings with low hardness and high susceptibility to scratching. The SiO2 nanoparticles were ground and modified using high-energy ball milling, during which the surface energy of nano-SiO2 particles rapidly increased as their particle size decreased. Different proportions of modified nano-SiO2 particles were added to the coating and cured into a film. The structure of the composite coating was analyzed via infrared spectroscopy, scanning electron microscopy, and X-ray diffraction, which confirmed the successful preparation of the composite coating. The mechanical and optical property tests of the coating were investigated. With a 5% nano-SiO2 content, the hardness of the coating reached 5H, whereas the adhesion was poor (2B), and the flexibility was 1. The overall comprehensive performance of the coating was best when the addition amount was 3%. The coating exhibited good hardness, flexibility, and adhesion. The hardness of the coating reached 4H, the adhesion was 4B, the flexibility was 5, the coating haze was 12.38 HZ, and the contact angle was 118°.

Prognostic utility of 99mTc-MIBI single photon emission computerized tomography myocardial perfusion imaging in patients with ischemia and non-obstructive coronary artery disease.

Objective: The aim of our study was to evaluate the prognostic value of gated SPECT MPI in non-obstructed coronary arteries (INOCA) patients, sought to stratify patients more accurately and thus derive more reliable prognostic information. Materials and methods: In total, 167 patients with INOCA were enrolled. The patients were divided into two groups according to their SSS. Patients were followed-up regularly in terms of major adverse cardiovascular event (MACE), including cardiac death, nonfatal myocardial infarction, stroke, re-hospitalization with angina pectoris, and recurrent angina pectoris. Kaplan-Meier curves and Cox's proportional hazards models were used to analyze survival and identify predictive factors. Results: Adverse cardiac events occurred in 33 cases (19.8%). The rate of MACE was higher in the summed stress score (SSS) ≥4 group than in the SSS 0-3 group (30.1% vs. 9.5%, respectively, P = 0.001) and MACE-free survival was lower (annual MACE-free rates of 87.5% vs. 96.2%, respectively, P = 0.003). Event-free survival was consistently higher in patients with normal arteries than in those with non-obstructive coronary artery disease (annual MACE-free rates of 96.1% and 88.4%, P = 0.035). When the SSS and the CAG results were combined, patients with normal coronary arteries (SSS 0-3) had the best prognosis and those with non-obstructive coronary artery stenosis (SSS ≥ 4) had the worst. However, the early prognosis of patients with non-obstructive coronary artery disease and SSS of 0-3 was comparable to that of patients with normal coronary arteries and SSS ≥ 4 (annual MACE-free rates of 100%, 94.6%, 93.1%, and 78.2%, respectively). Multivariate Cox's regression indicated that the SSS [hazard ratio (HR) = 1.126, 95% confidence interval (CI) 1.042-1.217, P = 0.003] and non-obstructive coronary artery disease (HR = 2.559, 95% CI 1.249-5.246, P = 0.01) were predictors of adverse cardiac events. Conclusion: SPECT MPI data were prognostic for INOCA patients, thus identifying groups at high risk. The long-term predictive efficacy of such data exceeded that of CAG data. A combination of the two measures more accurately stratified INOCA patients in terms of risk.

Sl-lncRNA47980, a positive regulator affects tomato resistance to Phytophthora infestans.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) involve in defense respond against pathogen attack and show great potentials to improve plant resistance. Tomato late blight, a destructive plant disease, is caused by the oomycete pathogen Phytophthora infestans, which seriously affects the yield and quality of tomato. Our previous research has shown that Sl-lncRNA47980 is involved in response to P. infestans infection, but its molecular mechanism is unknown. Gain- and loss-of-function experiments revealed that Sl-lncRNA47980 as a positive regulator, played a crucial role in enhancing tomato resistance to P. infestans. The Sl-lncRNA47980-overexpressing transgenic plants exhibited an improved ability to scavenge reactive oxygen species (ROS), decreased contents of endogenous gibberellin (GA) and salicylic acid (SA), and increased contents of jasmonic acid (JA), while silencing of Sl-lncRNA47980 showed an opposite trend in the levels of these hormones. Furthermore, it was found that Sl-lncRNA47980 could upregulate the expression of SlGA2ox4 gene through activation of the promoter of SlGA2ox4 to affect GA content. The increased expression of the tomato GA signaling repressor SlDELLA could activate JA-related genes and inhibit SA-related genes to varying degrees respectively. In addition, exogenous application of GA3 and GA synthesis inhibitor uniconazole could increase disease susceptibility of Sl-lncRNA47980-overexpressing plants and the resistance of Sl-lncRNA47980-silenced plants, respectively, to P. infestans. From thus, it was speculated that Sl-lncRNA47980 conferred tomato resistance to P. infestans, which was related to the decrease in endogenous GA content. Our study provided information to link Sl-lncRNA47980 with changes in ROS accumulation and phytohormone levels in plant immunity, thus providing a new candidate gene for tomato breeding.

Advances in the molecular imaging of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. It predisposes to adverse outcomes such as nephrotoxicity and cardiovascular damage, which are mediated by direct harm from hypertension to the target organs. Accurate subtype diagnosis and localization are crucial elements in choosing the type of treatment for PA in clinical practice since the dominant side of aldosterone secretion in PA affects subsequent treatment options. The gold standard for diagnosing PA subtypes, adrenal venous sampling (AVS), requires specialized expertise, the invasive nature of the procedure and high costs, all of which delay the effective treatment of PA. Nuclide molecular imaging is non-invasive and has wider applications in the diagnosis and treatment of PA. This review aims to provide a summary of the application of radionuclide imaging in the diagnosis, treatment management and prognostic assessment of PA.

The value of Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET/CT and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT in the detection of thyroid cancer lesions: a prospective head-to-head comparison.

OBJECTIVE: Thyroid cancer is increasing in incidence. Prostate-specific membrane antigen (PSMA) targeted radionuclide imaging and treatment demonstrated remarkable value in prostate cancer patients. Studies have shown that PSMA is also expressed in thyroid cancer. Our purpose is to evaluate the clinical usefulness of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of thyroid cancer. METHODS: We enrolled 23 DTC and 17 RAIR-DTC patients prospectively. All patients underwent [68Ga]Ga-PSMA-11 PET/CT and 2-[18F]FDG PET/CT. PSMA expression was determined by immunohistochemistry on histological samples of lymphatic metastasis of 12 patients. We compared the detection rates and semi-quantitative parameters between [68Ga]Ga-PSMA-11PET/CT and 2-[18F]FDG PET/CT. RESULTS: A total of 72 lesions were detected. Detection rates of DTC and RAIR-DTC by [68Ga]Ga-PSMA-11 PET/CT were lower than those by 2-[18F]FDG PET/CT (60.00% vs 90.00%, p = 0.004; 59.38% vs 96.88%). Compared with DTC, RAIR-DTC had higher semi-quantitative parameters of 2-[18F]FDG PET/CT. There was no significant difference in semi-quantitative parameters of [68Ga]Ga-PSMA-11 PET/CT between DTC and RAIR-DTC. Immunohistochemistry showed a significantly higher PSMA expression for RAIR-DTC than for DTC. However, there was no significant correlation between PSMA expression and SUVmax on 68Ga-PSMA [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT can detect thyroid cancer metastases but its detection rate was lower than that of 2-[18F]FDG PET/CT. There was a difference in PSMA expression levels between DTC and RAIR-DTC, but the difference was not reflected on [68Ga]Ga-PSMA-11 PET/CT. ADVANCES IN KNOWLEDGE: [68Ga]Ga-PSMA-11 PET/CT has potential value in the diagnosis of thyroid cancer. [68Ga]Ga-PSMA-11 PET/CT could screen out patients who may benefit from PSMA targeted radionuclide therapy.

miR-138-5p targets MCU to inhibit mitochondrial biogenesis and colorectal cancer growth.

miR-138-5p has been identified as a novel cancer-related miRNA molecule in a variety of malignancies. However, the functions and mechanisms underlying miR-138-5p in colorectal carcinoma (CRC) remains largely unknown. In the present study, we analysed the biological effects and clinical significance of miR-138-5p in CRC. miR-138-5p expression was analysed by quantitative real-time PCR in CRC tissues and cell lines. The effects of miR-138-5p on CRC cell growth was detected by cell proliferation, colony formation, cell cycle and cell apoptosis assays in vitro and in vivo. Our data showed that miR-138-5p was significantly downregulated in CRC. Downregulated miR-138-5p was related with poor prognosis in patients with CRC. miR-138-5p suppressed CRC growth but promoted cell death both in vitro and in vivo. Online predictions and integrated experiments identified that miR-138-5p targeted MCU, and downregulated miR-138-5p promoted mitochondrial biogenesis in CRC. In the light of the underlying mechanisms, our results indicated that downregulated miR-138-5p led to increased expression of MCU, which subsequently increased the production of ROS to promote CRC growth. Our results indicated that downregulated miR-138-5p strengthened mitochondrial biogenesis through targeting MCU, thus contributing to CRC cell growth, which may provide a potential therapeutic target for CRC.

Unveiling the secrets of non-coding RNA-encoded peptides in plants: A comprehensive review of mining methods and research progress.

Non-coding RNAs (ncRNAs) are not conventionally involved in protein encoding. However, recent findings indicate that ncRNAs possess the capacity to code for proteins or peptides. These ncRNA-encoded peptides (ncPEPs) are vital for diverse plant life processes and exhibit significant potential value. Despite their importance, research on plant ncPEPs is limited, with only a few studies conducted and less information on the underlying mechanisms, and the field remains in its nascent stage. This manuscript provides a comprehensive overview of ncPEPs mining methods in plants, focusing on prediction, identification, and functional analysis. We discuss the strengths and weaknesses of various techniques, identify future research directions in the ncPEPs domain, and elucidate the biological functions and agricultural application prospects of plant ncPEPs. By highlighting the immense potential and research value of ncPEPs, we aim to lay a solid foundation for more in-depth studies in plant science.

Clinical application of 18F-FCH PET/CT in the diagnosis and treatment of hyperparathyroidism.

Objective: We evaluated the difference in parathyroid visualization on 18F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT. Methods: This retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent 18F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses. Results: Dual-time 18F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783). Conclusion: The quantitative parameters of 60min 18F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.

Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms.

BACKGROUND: Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats. METHODS: The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-ß/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-ß/Smad3 pathway at the cellular level. RESULTS: The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-ß/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-ß/Smad3 pathway. CONCLUSION: EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-ß/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.

Annual review of KRAS inhibitors in 2022.

Kirsten rat sarcoma viral (KRAS) oncogene is the most commonly mutated isoform of RAS, accounting for 85% of RAS-driven human cancers. KRAS functioning as a signaling hub participates in multiple cellular signaling pathways and regulates a variety of critical processes such as cell proliferation, differentiation, growth, metabolism and migration. Over the past decades, KRAS oncoprotein has been considered as an "undruggable" target due to its smooth surface and high GTP/GDP affinity. The breakthrough in directly targeting G12C mutated-KRAS and recently approved covalent KRASG12C inhibitors sotorasib and adagrasib broke the myth of KRAS undruggable and confirmed the directly targeting KRAS as one of the most promising strategies for the treatment of cancers. Targeting KRASG12C successfully enriched the understanding of KRAS and brought opportunities for the development of inhibitors to directly target other KRAS mutations. With the stage now set for a new era in the treatment of KRAS-driven cancers, the development of KRAS inhibitors also enters a booming epoch. In this review, we overviewed the research progress of KRAS inhibitors with the potential to treat cancers covering articles published in 2022. The design strategies, discovery processes, structure-activity relationship (SAR) studies, cocrystal structure analysis as well as in vitro and in vivo activity were highlighted with the aim of providing updated sight to accelerate the further development of more potent inhibitors targeting various mutated-KRAS with favorable drug-like properties.

Prognostic role of pretreatment 18F-FDG PET/CT and hematological parameters in relapsed/refractory Hodgkin lymphoma patients treated with immune checkpoint inhibitors and chemotherapy: a dual-center cohort study.

BACKGROUND: The combination of anti-programmed death-1 antibodies and chemotherapy is effective; however, there are no reliable outcome prediction factors. We investigated the prognostic factors based on 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) quantitative and hematological parameters to predict progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients treated with immune checkpoint inhibitors (ICIs) and chemotherapy. METHODS: This retrospective study included 31 patients who underwent 18F-FDG PET/CT before and during treatment. Pretreatment metabolic and hematological parameters were evaluated using Cox regression analysis to identify predictors of PFS. Based on the cut-off values calculated using the receiver operating characteristic (ROC) curve, patients were classified into low-, intermediate-, and high-risk groups. Kaplan-Meier curves and the log-rank test were used to compare survival differences between the groups. RESULTS: Cox multivariable analysis indicted that the treatment response based on Lactate dehydrogenase (LDH), Lugano classification and SUVmax were independent predictors of PFS (P = 0.004, 0.007 and 0.039, respectively). The optimal cut-off values for SUVmax and LDH were 11.62 and 258.5 U/L, respectively (P < 0.01). Survival curves showed that LDH ≥ 258.5U/L and SUVmax ≥ 11.62 were correlated to shorter PFS (P < 0.001, P = 0.003, respectively). The differences in PFS between the low-, intermediate-, and high-risk groups were statistically significant (P = 0.0043). CONCLUSION: In R/R cHL patients treated with ICIs and chemotherapy, Lugano classification, SUVmax, and LDH were significantly correlated with PFS. The combination of metabolic and hematological parameters predicts PFS and may help to improve patient selection.

Role of metformin in inflammation.

BACKGROUND: Metformin has good anti-hyperglycemic effectiveness, but does not induce hypoglycemia，is very safe, and has become the preferred drug for the treatment of type 2 diabetes. Recently, the other effects of metformin, such as being anti-inflammatory and delaying aging, have also attracted increased attention. METHODS AND RESULTS: The relevant literatures on pubmed and other websites for reading, classification and sorting, and did not involve any animal experiments. CONCLUSION: Metformin has anti-inflammatory effects through multiple routes, which provides potential therapeutic targets for certain inflammatory diseases, such as neuroinflammation and rheumatoid arthritis. In addition, inflammation is a key component of tumor occurrence and development ; thus, targeted inflammatory intervention is a significant benefit for both cancer prevention and treatment. Therefore, metformin may have further potential for inflammation-related disease prevention and treatmen. However, the inflammatory mechanism is complex; various molecules are connected and influence each other. For example, metformin significantly inhibits p65 nuclear translocation, but pretreatment with compound C, an AMPK inhibitor, abolishes this effect, and silencing of HMGB1 inhibits NF-κB activation . SIRT1 deacetylates FoxO, increasing its transcriptional activity . mTOR in dendritic cells regulates FoxO1 via AKT. The interactions among various molecules should be further explored to clarify their specific mechanisms and provide more direction for the treatment of inflammatory diseases, as well as cancer.