Butyrate ameliorates colorectal cancer through regulating intestinal microecological disorders.

The occurrence and progression of colorectal cancer (CRC) are closely related to intestinal microecological disorders. Butyrate, the representative of short chain fatty acids, possess anti-inflammatory and antioxidant effects, and its antitumor effect has been gradually paid attention to. In this study, azoxymethane/dextran sodium sulfate induced mouse CRC model was used to explore the role and mechanism of butyrate in regulating colon cancer and its intestinal microecological balance. Outcomes exhibited that butyrate alleviated weight loss, disease activity index, and survival in CRC mice and inhibited tumor number and progression. Further research revealed that butyrate restrained the aggregation of harmful while promoting the colonization of beneficial flora, such as Actinobacteriota, Bifidobacteriales and Muribaculacea through 16S rDNA sequence analysis. This study confirmed that butyrate can ameliorate CRC by repairing intestinal microecology, providing ideas and evidence for chemical prophylactic agents, such as butyrate to remedy tumors and regulate tumor microbiota.

hucMSCs Attenuate IBD through Releasing miR148b-5p to Inhibit the Expression of 15-lox-1 in Macrophages.

Mesenchymal stem cells (MSCs) exert powerful immunosuppression in inflammatory bowel disease (IBD). Macrophages are the dominant inflammatory cells in enteritis regulated via MSCs. However, the roles of macrophages in the process of MSCs attenuating IBD and the mechanisms of MSCs regulating macrophages are largely unknown. In this study, DSS- (dextran sulfate sodium salt-) induced IBD in macrophage-depleted models of CD11b-DTR mice was used to study the relationship between hucMSCs (human umbilical cord mesenchymal stromal cells) and macrophage. Body weights, disease activities, and pathological changes were documented to assess the therapeutic effects of hucMSCs. Furthermore, hucMSCs transfected with miR148b-5p mimics and miR148b-5p inhibitors were cocultured with LPS-induced RAW264.7 cells to investigate the role of miR148b-5p in hucMSC-regulated colitis. The outcome indicated that hucMSCs attenuated the IBD by downregulating 15-lox-1 expression in macrophages. Further findings pointed out that hucMSCs transfected with miR148b-5p mimics could be elevated to promote the tissue repair and inhibit the expression of 15-lox-1 but failed to perform the function of easing enteritis when treated with miR148b-5p inhibitors. In conclusions, we propose that hucMSCs attenuate IBD by releasing miR148b-5p to inhibit the expression of 15-lox-1 in macrophages.

Molecular species determination of oligosaccharides and glycoconjugates in soybean lecithin powders.

BACKGROUND: Oligosaccharides and glycoconjugates in soybean lecithin powder are very important for the properties and functions of the materials that contain it. Oligosaccharides can trigger infusion reactions and color changes in soybean lecithin during medical injections; glycoconjugates in the form of glycolipids can also change the physical behavior of lecithin. The molecular components of oligosaccharides and glycoconjugates in soybean lecithin powder were studied in this paper. RESULTS: Three oligosaccharides and 21 glycoconjugates were verified in soybean lecithin powders for the first time. Raffinose, sucrose, and stachyose were detected as the principal components of oligosaccharides by high-performance liquid chromatography (HPLC). Twenty-one glycoconjugates, including four steryl glucosides (SG), 13 acyl steryl glucosides (ASG), one digalactosyl diacylglycerol (DGDG), one monogalactosyl diacylglyceride (MGDG), one glucocerebroside (Glucer), and one glucose palmitate were analyzed by gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and RP-UPLC-Q-TOF-ESI-MS. Glycoconjugates were constructed in soybean lecithin powder after separation by column chromatography, thin-layer chromatography, and color reactions. CONCLUSION: The determination of molecular species of oligosaccharides and glycoconjugates provided a new direction for the exploration of novel functions and uses of soybean lecithin powder. © 2018 Society of Chemical Industry.

Evaluation system construction and factor impact analysis of silica-gel adsorption to extract phytosterol glycosides from soybean lecithin powder.

BACKGROUND: Soybean lecithin powders are good sources of phytosterol glucosides (PGs) containing acyl-sterylglycosides (ASGs) and sterylglucosides (SGs), but PG extraction from soybean lecithin powder is difficult due to the solubilizing property of phospolipids. To comprehensively utilize soybean lecithin resources, an evaluation system construction and factor impact analysis of PG extraction by silica-gel adsorption was investigated in this article. RESULTS: With high-performance liquid chromatography (HPLC) as the main experimental analysis method, software such as SIMICA and SPSS were applied to construct an evaluation system of PG extraction. Different from scores plot in SIMICA for distinguishing samples in chloroform from others, the loading plot and binary variant correlation analysis of all indicators in PG extraction were brought to confirm four evaluation indicators containing PG purity, ASG recovery, SG recovery and phospholipid recovery. In the factor impact analysis, four times elution from silica-gel sediment was enough to achieve a PG product with least reagent waste, while SPW in petroleum ether at 50 mg mL-1 with 1:3 silica-gel dosage (lecithin/silica-gel, w/w) was then determined as the optimum of single factors. CONCLUSION: All studies in this article were of great significance, as they laid foundations for research of PG extraction procedure, as well as PG industrial production, facilitating the comprehensive utilization of lecithin resources. © 2019 Society of Chemical Industry.

Construction of Fluorescein Isothiocyanate-Labeled MSNs/PEG/Lycorine/Antibody as Drug Carrier for Targeting Prostate Cancer Cells.

Lycorine possesses various pharmacological effects, including anti-tumor, antiviral, anti-malarial and anti-inflammatory properties, as well as a potential therapeutic against prostate cancer cells. Therefore, a drug carrier of lycorine with good biocompatibility, high drug loading capacity and good release ability is required to develop to gain maximum benefit from lycorine to target cancer cells. In this study, MSNs labeled with FITC and PEG were synthesized. These FITC-labeled MSNs/PEG/Lycorine/Antibody were loaded with lycorine and anti-EpCAM antibody, and analyzed for endocytosis, biocompatibility, drug loading and release ability. Furthermore, the effects of FITC-labeled MSNs/PEG/Lycorine/Antibody on PC-3M cell line were also investigated. The results revealed that the FITC-labeled MSNs/PEG/Lycorine/Antibody contained excellent biocompatibility, as well as efficiently penetrated into cancer cells. Moreover, the FITC-labeled MSNs/PEG/Lycorine/Antibody nano-composites exhibited excellent drug release ability and induced PC-3M cell death more quickly, as compared to the free lycorine, even at relatively lower concentrations. In conclusion, the FITC-labeled MSNs/PEG/Lycorine/Antibody developed in this study could be used as promising candidates of drug carriers of lycorine for cancer chemotherapy with maximization of anticancer efficacy and reduction of the undesirable side effects to normal cells.

Crosstalk between mesenchymal stem cells and macrophages in inflammatory bowel disease and associated colorectal cancer.

Mesenchymal stem cells (MSCs) are attractive seed cells for immunotherapy, tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities, diverse immunoregulatory functions and ease of isolation from a wide range of tissues. MSCs exert their immunoregulatory effect on immune cells via cell-to-cell contact and paracrine mechanisms. In turn, MSCs can also be modulated by immune cells. Macrophages are constantly present in the mucosa of the intestinal tract of mammals and play an important role in the development and progression of inflammatory bowel disease (IBD), a chronic and recurrent inflammatory disease of the gastrointestinal tract characterized by idiopathic mucosal inflammation. The increased morbidity and mortality of IBD have made it a disease hard to cure in the clinic. MSCs have emerged as an important tool for IBD therapy due to their abilities to differentiate into enterocyte-like cells and regulate inflammatory cells, especially macrophages. In this review, we discuss the recent advances in the interaction between MSCs and macrophages in diseases, with an emphasis on IBD. We propose that an optimized MSC-based therapy would provide a novel strategy for the treatment of IBD and the prevention of IBD-associated colorectal cancer (CRC).

Superior component compositions and antioxidant activity of Volvariella volvacea oil compared to those of Agrocybe cylindracea and two Lentinula edodes oils.

The biological activity of an oil not only depends on its fatty acid composition but also the lipid composition and trace components. In this paper, to select the optimal mushroom oil, the component compositions (fatty acids, lipids, polyphenols, flavones, tocopherols, and unsaponifiable matters) and antioxidant activities in vitro of four mushroom oils (Agrocybe cylindracea, two Lentinula edodes, and Volvariella volvacea) were investigated and compared. The results showed that the four tested oils had the same fatty acid composition in different amounts, but the lipid component, minor components, and free radical scavenging activity in the tested oils varied widely depending on the type of mushroom. Overall, Volvariella volvacea oil was considered superior to the other three tested oils, as it had the largest contents of polar lipids, diglycerides, polyunsaturated fatty acids (74.38%), unsaponifiable matter (319.09 mg/kg), total phenols (124.08 mg/100 g), tocopherols (139.86 mg/100 g), as well as the highest ABTS and FRAP values (349.45 and 3801.70 µmol Trolox/100 g). This finding suggests that Volvariella volvacea oil is a promising resource that should be further researched.

Induction immunochemotherapy followed by definitive chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a multi-institutional retrospective cohort study.

This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p < 0.001). Patients with concurrent CRT demonstrated markedly improved PFS (p = 0.012) and OS (p = 0.017) than those undergoing sequential CRT. Additionally, those with a programmed-death ligand 1 (PD-L1) expression of 50% or higher showed significantly elevated ORRs (72.2% vs. 47.2%, p = 0.011) and superior OS (median 44.8 vs. 28.6 months, p = 0.004) compared to patients with PD-L1 expression below 50%. Hematologic toxicities were the primary severe adverse events (grade ≥ 3) encountered, with no unforeseen treatment-related toxicities. Thus, induction immunochemotherapy followed by definitive CRT demonstrated encouraging efficacy and tolerable toxicities for unresectable LA-NSCLC.

Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

Choline Phosphate-Grafted Nanozymes as Universal Extracellular Vesicle Probes for Bladder Cancer Detection.

Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.

TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases.

TRPV1 is a non-selective channel receptor widely expressed in skin tissues, including keratinocytes, peripheral sensory nerve fibers and immune cells. It is activated by a variety of exogenous or endogenous inflammatory mediators, triggering neuropeptide release and neurogenic inflammatory response. Previous studies have shown that TRPV1 is closely related to the occurrence and/or development of skin aging and various chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis, rosacea, herpes zoster, allergic contact dermatitis and prurigo nodularis. This review summarizes the structure of the TRPV1 channel and discusses the expression of TRPV1 in the skin as well as its role of TRPV1 in skin aging and inflammatory skin diseases.

The interaction of peptide inhibitors and Aß protein: Binding mode analysis, inhibition of the formation of Aß aggregates, and then exert neuroprotective effects.

Introduction: The misfolding and aggregation of ß-amyloid (Aß) easily form Aß fibers, which are continuously deposited in the brain, leading to the massive generation of amyloid plaques, severely destroying neuronal connections, and promoting Alzheimer's disease (AD) The occurrence and development of AD is one of the pathogenesis of AD. There is an urgent need to develop inhibitors against Aß aggregation, which is hopefully a potential way to treat AD. Methods: In this study, we first found the crystal structure of the Aß1-42 receptor protein from the RCSB PDB protein structure database and used the SYBYL X2.0 software for molecular docking, and then used the Peptide Ranker, Innovagen, DPL, and ToxinPred online websites to perform peptides. Predict the activity score, toxicity and water solubility, and then calculate the affinity constant KD value of polypeptide and Aß through Surface Plasmon Resonance (SPR) experiment. Subsequently, the CCK-8 kit method was used to determine the toxicity of different concentrations of peptides (3.125, 6.25, 12.5, 25, 50, 100, 200 µM) to PC12 cells, and then the peptides and Aß according to different concentration ratios (1:4, 1:2, 1:1, 1:0.5, 1:0.25, 0:4), this method is also used to detect the effect of peptides on Aß-induced neurotoxicity. The thioflavin T (ThT) fluorescence method was used to detect the effects of peptides (50 µM) on Aß (25 µM) aggregation inhibitory effect. Results: The results showed that the CScore of YVRHLKYVRHLK peptide molecule docking was 10.0608, the predicted activity score was 0.20, and the KD value was 5.385 × 10-5. The ThT and CCK-8 kit method found that the peptide itself is less toxic to PC12 cells at a concentration of 50 µM, and it has a significant inhibitory effect on the formation of Aß1-42 aggregates when incubated with Aß1-42 at a ratio of 1:1 (p < 0.05) and can significantly reduce the PC12 cytotoxicity induced by Aß1-42 (p < 0.05). Conclusion: In conclusion, the polypeptide YVRHLKYVRHLK designed in this study has a neuroprotective effect on PC12 cytotoxicity induced by Aß1-42. Graphical Abstract.

Transient Receptor Potential Vanilloid1 (TRPV1) Channel Opens Sesame of T Cell Responses and T Cell-Mediated Inflammatory Diseases.

Transient receptor potential vanilloid1 (TRPV1) was primarily expressed in sensory neurons, and could be activated by various physical and chemical factors, resulting in the flow of extracellular Ca2+ into cells. Accumulating data suggest that the TRPV1 is expressed in some immune cells and is a novel regulator of the immune system. In this review, we highlight the structure and biological features of TRPV1 channel. We also summarize recent findings on its role in modulating T cell activation and differentiation as well as its protective effect in T cell-mediated inflammatory diseases and potential mechanisms.

Comparison of stereotactic body radiotherapy and radiofrequency ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

Background: Stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are recommended for patients with inoperable early-stage non-small cell lung cancer (NSCLC), with both offering promising results. However, it is largely unknown which of these two treatment modalities provides superior benefits for patients. Therefore, this systematic review and meta-analysis compared clinical outcomes and safety between SBRT and RFA in patients with inoperable early-stage NSCLC. Methods: Eligible studies published between 2001 and 2020 were obtained through a comprehensive search of the PubMed, Medline, Embase, and Cochrane Library databases. Original English-language studies on the treatment of early-stage NSCLC with SBRT or RFA were included. Local control (LC) rates, overall survival (OS) rates, and adverse events were obtained by pooled analyses. Results: Eighty-seven SBRT studies (12,811 patients) and 18 RFA studies (1,535 patients) met the eligibility criteria. For SBRT, the LC rates (with 95% confidence intervals) at 1, 2, 3, and 5 years were 98% (97-98%), 95% (95-96%), 92% (91-93%), and 92% (91-93%), respectively, which were significantly higher than those for RFA [75% (69-82%), 31% (22-39%), 67% (58-76%), and 41% (30-52%), respectively] (P<0.01). There were no significant differences in short-term OS between SBRT and RFA [1-year OS rate: 87% (86-88%) versus 89% (88-91%), P=0.07; 2-year OS rate: 71% (69-72%) versus 69% (64-74%), P=0.42]. Regarding long-term OS, the 3- and 5-year OS rates for SBRT were 58% (56-59%) and 39% (37-40%), respectively, which were significantly (P<0.01) superior to those for RFA [48% (45-51%) and 21% (19-23%), respectively]. The most common complication of SBRT was radiation pneumonitis (grade ≥2), making up 9.1% of patients treated with SBRT, while pneumothorax was the most common complication of RFA, making up 27.2% of patients treated with RFA. Discussion: Compared with RFA, SBRT has superior LC and long-term OS rates but similar short-term OS rates. Prospective randomized trials with large sample sizes comparing the efficacy of SBRT and RFA are warranted.

Self-administration of complex decongestive therapy facilitated by the mobile application WeChat improves lymphedema and quality of life in breast cancer survivors: an observational study.

Background: Lymphedema is the most common complication of breast cancer patients. Complex decongestive therapy (CDT) is often recommended but the efficacy varies due to the complexity of management. This study investigated a novel model of CDT based on a mobile application with the aim of improving the management of lymphedema in China. Methods: We developed a novel model of CDT for breast cancer survivors with lymphedema, including 5 days of CDT therapy with training provided by medical staff in the outpatient clinic and 3 weeks of self-administrated CDT with daily online instructions during phase I, and a life-long maintenance treatment with online instructions once a week for phase II, which delivered by WeChat public accounts. The breast cancer and lymphedema symptom experience index (BCLE-SEI) and the Short-Form Health Survey (SF-36) were used to assess lymphatic symptoms and quality of life. Arm volume and lymphatic symptoms were assessed at baseline, and at 5 days, 1 month, and 3 months post-treatment. The quality of life was assessed at baseline and at 3 months post-treatment. Results: A total of 88 patients with lymphedema were recruited, of whom, 61 followed the protocols and were further analyzed for this study. The mean relative excess arm volume (EAV) was reduced from a baseline value of 30.72% to 22.05%, 18.46%, and 16.67% at 5 days, 1 month, and 3 months post-therapy, respectively (P=0.000). The BCLE-SEI scores of lymphatic pain, heaviness, and impaired limb mobility were all significantly improved after 3 months of treatment (P<0.05). Moreover, according to the subscale of SF-36, the general health and vitality were significantly improved after 3 months of therapy (56.64 vs. 62.93, P=0.008; and 64.26 vs. 70.08, P=0.024, respectively). Conclusions: The proposed model of CDT based on the mobile application WeChat achieved promising outcomes. The volume of the affected arm, the lymphedema symptoms, and the quality of life were all significantly improved.

Effects of Weaning Modes on the Intestinal pH, Activity of Digestive Enzymes, and Intestinal Morphology of Piglets.

The present study investigated the effects of weaning modes on the intestinal pH, digestive enzyme activities, and intestinal morphology of piglets. A total of 27 litters of "Duroc boars × Landrace × Large White" piglets were selected and randomly divided into three groups. Those groups were the conventional weaning group (C), the odorant spray group (S), and the weaning-after-mixing group (M), with three repeats in each group and three litters in each repeat. The experiment began seven days before weaning, and ended seven days after weaning. The piglets were euthanized on the eighth day after weaning, and the jejunum and ileum tissues and contents were sampled. The pH and enzyme activities of the intestinal contents were determined, and the intestinal morphologies were revealed using H&E staining. It was concluded that a 2% glutaraldehyde spray on the body surfaces of piglets after weaning could increase average weight after nursery, lower intestinal pH, increase the activities of digestive enzymes, improve intestinal morphology, and relieve weaning stress. It was also found that weaning after mixing could increase the average weight after nursery, lower intestinal pH, improve intestinal morphology, and reduce weaning stress.

Postoperative radiotherapy improves survival of patients with ypN2 non-small cell lung cancer after neoadjuvant chemotherapy followed by surgery - A propensity score matching study of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: For patients with ypN2 non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgery (NCS), the role of postoperative radiotherapy (PORT) is unclear. The aim of our study was to evaluate the effect of PORT on survival of ypN2 NSCLC patients after NCS. METHODS: Between 2004 and 2015, patients with ypN2 NSCLC after NCS were filtrated from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance the baseline characteristics of the PORT and non-PORT groups. Kaplan-Meier method and Cox proportional hazards models were adopted to estimate overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 257 patients who met the criteria were included in the study. After PSM, 115 patients remained in each group. The survival of patients in the PORT group was significantly better than those in the non-PORT group. Median OS was 36 months vs. 26 months, and 5-year OS rate was 40.5% vs. 21.0% (p = 0.002). The median CSS was 38 months vs. 27 months, and the 5-year CSS rate was 43.7% vs. 22.1% (p < 0.001). Multivariable analysis showed that PORT was an independent prognostic factor for OS (HR = 0.59, 95% CI: 0.43-0.82, p = 0.001) and CSS (HR = 0.56, 95% CI: 0.41-0.78, p = 0.001). Subgroup analysis showed that patients in the following subgroups could benefit from PORT: age ≤ 70, diagnosed in the later period (2010-2015), white race, squamous cell carcinoma, grade III-IV, lobectomy, stage T3-4, or with positive regional nodes ≤3 or > 3. CONCLUSIONS: For patients with ypN2 NSCLC after NCS, PORT significantly improves OS and CSS. These results need to be confirmed by further randomized studies.

The efficacy and safety of Zengxiao Jiandu decoction combined with definitive concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a randomized, double-blind, placebo-controlled clinical trial.

Background: Traditional Chinese medicine (TCM) makes a synergistic and attenuative effect when combined with chemoradiotherapy. However, strong evidence-based studies are lacking. The study sought to investigate whether Zengxiao Jiandu decoction as an adjunctive therapy is superior to definitive concurrent chemoradiotherapy (DCCRT) alone in unresectable, locally advanced (LA), stage III non-small cell lung cancer (NSCLC). Methods: Patients with unresectable LA-NSCLC were randomly assigned to receive DCCRT either combined with Zengxiao Jiandu decoction (TCM arm) or placebo therapy (Control arm), by computer-generated random assignment lists using a central randomization system. The patients were routinely followed-up every 3 months for the first 2 years after the therapy, and every 6 months for the subsequent 3 years, or earlier if clinically indicated. The primary endpoint was grade ≥3 chemoradiotherapy-related toxicities, while secondary endpoints included the completion rate of chemoradiotherapy, the clinical objective response rate (ORR), and survival. The placebo achieved full consistency in color, aroma, taste and appearance with the Zengxiao Jiandu decoction. Results: From February 2019 to December 2020, 163 patients were randomly allocated to TCM arm (n=82) or Control arm (n=81). Fifty-nine (72.0%) patients in TCM arm finished chemoradiotherapy per protocol and 79 (96.3%) received protocol-specified Zengxiao Jiandu decoction. Forty-two patients in Control arm finished chemoradiotherapy per protocol. The incidence of grade ≥3 chemoradiotherapy-related toxicities was higher in Control arm than TCM arm (44.4% vs. 31.7%, P=0.094). Grade ≥3 radiation pneumonitis occurred more frequently in Control arm than TCM arm (13.6% vs. 3.7%, P=0.024). The completion rate of the protocol-specified chemotherapy was significantly higher in TCM arm than Control arm (79.3% vs. 64.2%, P=0.033), but the completion rates of the definitive-dose radiotherapy were similar. There were no significant differences in ORR between the 2 arms. The progression-free survival (PFS) of TCM arm was significantly better than Control arm (median PFS, 12.0 vs. 9.0 months, P=0.035). However, Zengxiao Jiandu decoction was not found to produce any significant benefit in overall survival. Conclusions: The Zengxiao Jiandu decoction adjunctive therapy, as compared to DCCRT alone, reduced grade ≥3 radiation pneumonitis, improved the completion rate of DCCRT, and prolonged PFS for unresectable LA-NSCLC. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031667.

The association between the ERCC1/2 polymorphisms and radiotherapy efficacy in 87 patients with non-small cell lung cancer.

BACKGROUND: This study sought to investigate the association between the ERCC1/2 single-nucleotide polymorphisms (SNPs) and the efficacy of radiotherapy and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: We examined 6 SNPs in the ERCC1 and ERCC2 genes in 87 consecutive patients with NSCLC who were treated with definitive radiotherapy. The objective remission rates (ORR), overall survival (OS), and progressive-free survival (PFS) were assessed. A Cox regression analysis was conducted to analyze the independent factors related to death and recurrence. RESULT: Patients with the G allele had better OS than patients with the A allele, and there was a statistical difference between the two groups (30.9 vs. 16.2 months; P=0.003). Patients with the AA genotype had significantly worse OS than patients with the AG or GG genotypes (6.8 vs. 19.8 vs. 30.9 months, respectively; P=0.000). The median PFS of the G allele was 18.9 months, which was significantly better than that of the A allele (P=0.040). The median PFS of patients with the GG genotype, the AG genotype, and the AA genotype was 18.9, 11.3, and 5.1 months, respectively; the difference among the three groups was statistically significant (P=0.019). Patients with the G allele also had better PFS than those with the A allele (18.9 vs. 11.3 months, P=0.040). The multivariate cox proportional hazard analysis showed that the ERCC1 gene rs11615 was an independent survival indicator [HR: 1.623, 95% confidence interval (CI): 1.018-2.591, P=0.042] but not an independent recurrence indicator (HR: 1.497, 95% CI: 0.932-2.404, P=0.095). CONCLUSIONS: The ERCC1 rs11615 SNP may be a potential biomarker for predicting survival prognosis in Chinese NSCLC patients who have undergone definitive radiotherapy. Patients with the G allele had better OS than those with the A allele.

A Propensity-Matched Analysis of Survival of Clinically Diagnosed Early-Stage Lung Cancer and Biopsy-Proven Early-Stage Non-Small Cell Lung Cancer Following Stereotactic Ablative Radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been increasingly regarded as a reasonable option for early-stage lung cancer patients without pretreatment pathologic results, but the efficacy and safety in a Chinese population remains unclear. The aim of this study was to compare survival outcomes and toxicities between patients with clinically diagnosed early-stage lung cancer or biopsy-proven early-stage non-small cell lung cancer and to demonstrate the rationality of this treatment. MATERIAL AND METHODS: From May 2012 to December 2018, 56 patients with clinically diagnosed early-stage lung cancer and 60 patients with early-stage biopsy-proven were selected into non-pathological group and pathological group, respectively. Propensity score matching (PSM) was performed to reduce patient selection bias. Survival analysis with log-rank test was used to assess the differences of treatment outcomes, which included local control (LC), progression-free survival (PFS), and overall survival (OS). RESULTS: The median age was 76 (range 47-93) years, and the median follow-up time was 58.3 (range 4.3-95.1) months in the cohort without pathologic results. The median age was 74 (range 57-88) years, and the median follow-up time was 56.3 (range 2.6-94) months in the cohort with pathologic results. 45 matched-pair were analyzed. The 5-year LC, PFS, and OS rates in matched-pair patients with or without pathologic biopsy were 85.5% and 89.8%, 40.6% and 70.9%, and 63.2% and 76.1%, respectively. On Kaplan-Meier survival analysis after PSM analysis, there was no significant difference between patients with pathologic results versus patients with no pathologic results in terms of LC (P= 0.498) and OS (P=0.141). Of the matched-pair patients treated with SBRT, only 1 patient experienced grade 3 or above radiation pneumonitis. CONCLUSION: For early-stage lung cancer patients with medically inoperable or not suitable for invasive diagnosis, SBRT may be a good local treatment.