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Background Along with increasing research on acupuncture for chronic pain, the validity of sham acupuncture (SA) has also been argued. Methods Nine databases were searched for randomized controlled trials (RCTs) from the inception dates of the databases to July 5, 2022. With Markov Chain Monte Carlo methods, a Bayesian multiple-treatment network meta-analysis (NMA) with random-effects model was conducted. Results A total of 62 RCTs with 6,806 patients and four kinds of treatments (real acupuncture [RA], non-acupuncture [NA], penetrative SA [PSA], and non-penetrative SA [NPSA]) were included. The results indicated that both NPSA and PSA were not superior to NA in improving chronic pain (NPSA: mean difference [MD]= –4.77, 95% confidence interval [CI] –11.09 to 1.52; PSA: MD= –4.96, 95% CI –10.38 to 0.48). After NPSA and PSA were combined into the SA group, the weak trend of pain relief from SA was still not statistically significant (MD= –4.91, 95% CI –9.93 to 0.05). NPSA and PSA had similar effects (MD= 0.18, 95% CI –5.45 to 5.81). RA was significantly associated with pain relief, compared with NPSA and PSA (NPSA: MD= –12.03, 95% CI –16.62 to –7.41; PSA: MD= –11.85, 95% CI –15.48 to –8.23). The results were generally consistent regardless of pain phenotype, frequency, duration, acupuncture methods, analgesic intake, or detection bias. Conclusion These results suggested that acupuncture was significantly associated with reduced chronic pain. The two kinds of placebo acupuncture, NPSA and PSA, have similar effects. Both NPSA and PSA, with a weak but not significant effect, are appropriate to be inert placebo controls in RCTs for chronic pain. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bone metastasis attenuates efficacy of immune checkpoint inhibitors in NSCLC patients. • Bone metastasis negatively affects clinical outcomes irrespective of PD-L1 expression. • Bone metastatic NSCLC patients display "cold" immune characteristics. This study aimed to assess the clinical characteristics affecting outcomes after immune checkpoint inhibitors (ICI) therapies in non-small cell lung cancer (NSCLC) patients, and the underlying mechanism in tumor immune micro-environment (TIME). A total of 144 patients treated with ICI-based strategies were retrospectively analyzed. Expression of 10 immune antibodies in tumor tissues from other 60 untreated NSCLC patients were sequentially tested using multiplexed immunofluorescence (mIF) staining method. Correlation of clinical characteristics with ICI treatment outcomes and TIME characteristics were analyzed. Multivariate logistic and cox regression indicated that BoM negatively affected disease control rate (OR = 0.32, 95%CI: 0.13–0.82, P = 0.018), progression free survival (HR = 3.44, 95% CI:1.97–6.00, P < 0.001) and overall survival (HR = 3.24, 95% CI:1.62–6.50, P = 0.001), irrespective of programmed death-ligand 1 (PD-L1) expression. BoM patients were with significantly lower PD-L1, and this heterogeneity of TIME was then confirmed in the mIF staining, where 36 (61.0%) patients were clustered into immune-subtype A, with low expression of all the detected immune markers, similar to "cold" tumors, and 23 (39.0%) in cluster B with likely "hot" tumors. More patients in immune-subtype A were non-smokers (63.9% vs. 39.1% P = 0.063), with BoM (66.7% vs. 21.7%, P = 0.001), in stage IV(88.9% vs. 65.2%, P = 0.045), and with adenocarcinoma (91.7% vs. 69.6%, P = 0.037). Multivariate logistic regression indicated that BoM was independently associated with the "cold" immune characteristics (OR = 0.19, 95% CI:0.04–0.84, P = 0.028). Combination therapy with chemotherapy /antiangiogenesis or use of bisphosphonate during ICI treatment significantly improved clinical outcomes in BoM patients. BoM displays adverse impact on clinical outcomes after ICI treatments in NSCLC patients. The "cold" characteristics of TIME may be the underlying mechanism for the attenuated efficacy of ICIs in bone metastatic NSCLC patients. [ABSTRACT FROM AUTHOR]

Context: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy.Objectives: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients.Methods: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga.Results: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012).Conclusion: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA. [ABSTRACT FROM AUTHOR]

Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Objectives Droplet digital polymerase chain reaction (ddPCR) has shown sufficient concordance in detecting plasma epidermal growth factor receptor ( EGFR ) status in non-small cell lung cancer (NSCLC), compared to tumor tissues. However, the clinical significance of the quantitative plasma mutated EGFR concentration remains unknown. The purpose of this study was to explore the relationship of plasma mutated EGFR concentration with tumor burden in advanced NSCLC patients. Materials and methods Using ddPCR, plasma DNA samples prior to administration of therapies from 113 consecutive NSCLC patients were analyzed for EGFR L858R substitution and deletion of exon19 (ex19del). Plasma EGFR status was compared to tumor EGFR status to determine concordance. Then, we assessed the correlation of plasma mutated EGFR concentrations with tumor burden and other tumor characteristics. Results and conclusion Compared to tumor EGFR , the concordance rate of plasma and tissue EGFR status was 86.73%. Of the 64 patients who harbored tumor EGFR mutation, plasma mutated EGFR concentrations significantly correlated with number of metastatic sites (Spearman’s r = 0.4954, p < 0.0001), number of lesions (Spearman’s r = 0.4484, p = 0.0002), and sum of measurable lesions’ diameters (Spearman’s r = 0.3539, p = 0.0048). Number of metastatic sites was independently associated with mutated EGFR concentration in multiple linear regression. Besides, plasma mutated EGFR concentrations were significantly higher in those with extensive tumor burden (median concentration, 386.9 vs. 13.4 copies/mL; p < 0.0001) and stage IV disease (median concentration, 244.2 vs. 0 copies/mL; p = 0.0252). In conclusion, mutated plasma EGFR concentration determined by ddPCR analysis significantly correlated with tumor burden. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC) or Yang-heat (YH) syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression. In the 299 patients who had their EGFR gene tested, 45.24% YC (76/168) and 25.95% YH (34/131) patients had EGFR mutations (p=0.001). Among the 292 patients entered into the cluster analysis, 132 were classified into group A, with signs and symptoms similar to YC, whereas 160 group B patients were similar to YH. In the 281 patients with EGFR tested, 45.67% group A (58/127) and 28.57% group B patients (44/154) had EGFR mutations (p=0.003). The EGFR status was independently correlated with TCM syndrome type and classification by cluster analysis on multivariate logistic regression. NSCLC patients with YC were more likely to have EGFR gene mutations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highlights on key criteria to consider during LCOs establishment. • Comprehensive summary of molecules, compounds, and their function in LCOs 3D culture. • Potential applications and current challenges of LCOs. Lung cancer organoids (LCOs) have sprung up in more and more researching fields, because of their ability to recapitulate the three-dimensional structure and functions of the in vivo counterpart organs. However, the culture system for LCOs is still immature, resulting in limited success rate and low tumor purity when culturing LCOs. This is mainly due to the deficiency of an optimal formula of culture medium specially for LCOs. Various cytokines and small molecules have been added in the LCOs culturing system. Compound screening, considering both the mechanism of these molecules and the complexity of lung cancer types is warranted to optimize LCOs culture medium. As methods to culture LCOs increase in sophistication, this model will undoubtedly stand its ground in the coming years in every aspect of cancer researches, especially with major advantages in the field of personalized medicine and tumor microenvironment researches. [ABSTRACT FROM AUTHOR]

Objective Myonectin is one of the myokines and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM).The objective of this study was to investigate circulating serum myonectin levels in nondiabetes and T2DM and elucidate possible relationships between serum myonectin levels and metabolic parameters in patients with T2DM. Design A total of 362 Chinese patients with T2DM and 100 age- and sex-matched healthy controls were recruited in this study. Clinical characteristics, blood biochemistry, and circulating myonectin levels were measured by enzyme-linked immunosorbent assay. Results Circulating myonectin levels were significantly decreased in T2DM compared with controls. Obese nondiabetic controls had significantly lower serum myonectin levels compared with lean nondiabetic controls. In diabetic patients, serum myonectin concentrations were significantly negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting insulin (Fins), the homeostatic model assessment of insulin resistance (HOMA-IR), visceral fat area, and subcutaneous fat area. After adjusting for covariates, multivariate stepwise regression analysis demonstrated that BMI, LDL-C, TG, HOMA-IR, and visceral fat were the main independent predictors of low serum myonectin concentrations. Conclusions Circulating myonectin levels were decreased in T2DM patients and in obese subjects. Moreover, serum myonectin levels were correlated with metabolic markers of T2DM. These data suggest that myonectin may be a useful marker in predicting the development of obesity and T2DM. [ABSTRACT FROM AUTHOR]

Background: Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC.Methods: We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases.Results: A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%).Conclusion: Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape. [ABSTRACT FROM AUTHOR]

Chronic dietary high fructose leads to various kinds of undesirable metabolic effects. Apigenin, a naturally occurring plant flavone, is plentiful in fruits and vegetables. The aim of this study was to identify the protective effects of apigenin on metabolic syndrome and elucidate potential underlying mechanisms. The animal model was established by 4-weeks high fructose feeding. Insulin resistance was estimated by oral glucose tolerance test and homeostasis model assessment-insulin resistance index. Liver function was evaluated by serum AST and ALT, hepatic histopathological alternation, and lipid accumulation in the liver. The alterations of lipid profile was evaluated by TG, TC, LDL-C and HDL-C levels in serum. Administration of apigenin exerted beneficial effects through improving insulin resistance, alleviating liver injury, and inhibiting the alterations of lipid profile in high fructose-fed mice. In addition, apigenin potently facilitated the accumulation of Nrf2 nuclear translocation and accompanied by increasing HO-1 and NQO1 protein expressions, which are responsible for attenuating oxidative stress. Molecular docking results demonstrated that potential interaction of apigenin with the Nrf2-binding site in the Keap1 protein. In summary, we demonstrated that apigenin prevented high fructose-induced metabolic syndrome probably by inhibiting binding of Keap1 to Nrf2, and thus Nrf2 nuclear translocation, subsequently resulting in increased the expressions of anti-oxidative genes including HO-1 and NQO1. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects. High glucose (HG) cultured INS-1 cells were exposed to 50 μM of honokiol for 24, 48 and 72 h with or without IH intervention. T2DM rats were treated with honokiol and exposed to 80 s of IH followed by 160 s of normoxia for 8 weeks. The cell proliferation, apoptosis and oxidative stress were measured. Blood glucose, insulin, glucagon and HOMA-IR (Homeostasis model assessment -insulin resistence) were also detected, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by immunofluorescence staining and western blotting. Honokiol can reduce oxidative stress, cytotoxicity and apoptosis in the INS-1 cells of rats receiving HG treatment or both HG and IH treatment. IH can further aggravate pancreas dysfunction, cause a marked elevation in fasting blood glucose, glucagon, HOMA-IR and oxidative stress levels in DM rats. In addition, honokiol can effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in vivo and in vitro . These findings indicate that honokiol acts as a potent ROS scavenger via Nrf2/ARE pathway and effectively attenuates oxidative stress and improves pancreatic β cell function of DM rats under IH treatment. [ABSTRACT FROM AUTHOR]