Responses of microbial communities subjected to hydrodynamically induced disturbances in an organic contaminated site.

Organic contaminated sites have gained significant attention as a prominent contributor to shallow groundwater contamination. However, limited knowledge exists regarding the impact of hydrodynamic effects on microbially mediated contaminant degradation at such sites. In this study, we investigated the distribution characteristics and community structure of prokaryotic microorganisms at the selected site during both wet and dry seasons, with a particular focus on their environmental adaptations. The results revealed significant seasonal variations (P < 0.05) in the α-diversity of prokaryotes within groundwater. The dry season showed more exclusive OTUs than the wet season. The response of prokaryotic metabolism to organic pollution pressure in different seasons was explored by PICRUSt2, and enzymes associated with the degradation of organic pollutants were identified based on the predicted functions. The results showed that hormesis was considered as an adaptive response of microbial communities under pollution stress. In addition, structural equation models demonstrated that groundwater level fluctuations can, directly and indirectly, affect the abundance and diversity of prokaryotes through other factors such as oxidation reduction potential (ORP), dissolved oxygen (DO), and naphthalene (Nap). Overall, our findings imply that the taxonomic composition and functional properties of prokaryotes in groundwater in organic contaminated sites is influenced by the interaction between seasonal variations and characteristics of organic pollution. The results provide new insights into microbiological processes in groundwater systems in organic contaminated sites.

Helicobacter pylori-positive chronic atrophic gastritis and cellular senescence.

BACKGROUND: Chronic atrophic gastritis (CAG) is a pathological stage in the Correa's cascade, whereby Helicobacter pylori (H. pylori) infection is the primary cause. Cellular senescence is an inducing factor for cancer occurrence and cellular senescence is an obvious phenomenon in gastric mucosal tissues of H. pylori-positive CAG patients. METHODS: In this review, we collated the information on cellular senescence and H. pylori-positive CAG. RESULTS: At present, only a few studies have observed the effect of cellular senescence on precancerous lesions. In combination with the latest research, this review has collated the information on cellular senescence and H. pylori-positive CAG from four aspects- telomere shortening, DNA methylation, increased reacive oxygen species (ROS) production, and failure of autophagy. CONCLUSION: This is expected to be helpful for exploring the relevant mechanisms underlying inflammatory cancerous transformation and formulating appropriate treatment strategies.

Time-resolved fluorescence immunoassay (TRFIA) for the simultaneous detection of hs-CRP and lipoprotein(a) in serum.

Elevated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein(a) (Lp(a)) levels are associated with the development of native coronary atherosclerosis. We aimed to establish a new method for the simultaneous detection of hs-CRP and Lp(a) to predict the development of atherosclerosis. A one-step time-resolved fluorescence immunoassay (TRFIA) with europium(III) (Eu3+ ) or samarium(III) (Sm3+ ) labels was established, and the performance of this TRFIA (in terms of sensitivity, specificity, accuracy, and cutoff values) was evaluated using clinical serum samples and compared with those of registered kits. The sensitivity was 0.052 µg/ml for hs-CRP and 0.64 µg/ml for Lp(a). The intra-assay and inter-assay cross-reactivities (CVs) were very low, ranging from 2.05% to 4.67% for hs-CRP and from 2.42% to 6.43% for Lp(a). The CVs were very low (<0.34% and <2.65%, respectively) with five interferents. Additionally, there was a high Pearson coefficient between the present TRFIA method and the registered kits (R2 = 0.9967 and 0.9906, respectively). These data indicate that this study developed a TRFIA method that can be used for the quantitative detection of hs-CRP and Lp(a) in serum with high sensitivity, specificity, and accuracy. This TRFIA provides a new method for predicting the development of atherosclerosis.

Spatial distribution model of DEHP contamination categories in soil based on Bi-LSTM and sparse sampling.

Soil pollution is a serious threat to human life and development. Different remedial measures are applied to soils with different levels of contamination. The degree of soil contamination in different areas is generally evaluated and categorised based on the analysis of samples. Regional soil sampling sites are generally sparse because of the cost of sampling and other factors, which makes it difficult to accurately assess the extent of regional soil contamination. In this study, a spatial classification model was established for the Di(2-ethylhexyl) phthalate (DEHP) pollution level using a Bi-directional Long Short-Term Memory (Bi-LSTM) neural network considering that the sampling information gradually diminishes with increasing distance between the sampling and prediction points. In this study, a method is proposed for the prediction of the spatial distribution of soil pollution categories based on sparse samples. We also established a model for the spatial distribution of organic pollution categories. The analysis of an actual contaminated area shows that the DEHP concentrations at different locations can be effectively predicted with the proposed method by categorising the contamination levels of specific DEHP samples. The results show that the method can be used to classify the degree of light/severe DEHP contamination. The results are in good agreement with the actual situation, verifying the validity of the method. This method is important for the rapid assessment of the spatial distribution of soil contamination levels based on sparse sampling.

The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells.

Osteosarcoma (OS) is a malignancy that is becoming increasingly common in adolescents. OS stem cells (OSCs) form a dynamic subset of OS cells that are responsible for malignant progression and chemoradiotherapy resistance. The unique properties of OSCs, including self-renewal, multilineage differentiation and metastatic potential, 149 depend closely on their tumor microenvironment. In recent years, the likelihood of its dynamic plasticity has been extensively studied. Importantly, the tumor microenvironment appears to act as the main regulatory component of OS cell plasticity. For these reasons aforementioned, novel strategies for OS treatment focusing on modulating OS cell plasticity and the possibility of modulating the composition of the tumor microenvironment are currently being explored. In this paper, we review recent studies describing the phenomenon of OSCs and factors known to influence phenotypic plasticity. The microenvironment, which can regulate OSC plasticity, has great potential for clinical exploitation and provides different perspectives for drug and treatment design for OS.

microRNA-129 overexpression in endothelial cell-derived extracellular vesicle influences inflammatory response caused by myocardial ischemia/reperfusion injury.

Extracellular vesicles (EVs) have the potency to function as modulators in the process of myocardial ischemia/reperfusion (I/R) injury. This investigation was performed to decipher the mechanism of human umbilical vascular endothelial cells (HUVECs)-derived EVs in myocardial I/R injury with the involvement of microRNA-129 (miR-129). HUVECs-secreted EVs were collected and identified. An I/R mouse model was developed, and cardiomyocytes were used for vitro oxygen-glucose deprivation/reperfusion model establishment. Differentially expressed miRNAs in myocardial tissues after EV treatment were assessed using microarray analysis. The target relationship between miR-129 and toll-like receptor 4 (TLR4) was identified using a dual-luciferase assay. Gain- and loss-function studies regarding miR-129 were implemented to figure out its roles in myocardial I/R injury. Meanwhile, the activation of the nuclear factor-kappa-binding (NF-κB) p65 signaling and NOD-like receptor 3 (NLRP3) inflammasome was evaluated. EVs diminished the apoptosis of cardiomyocytes and the secretion of inflammatory factors, and all these trends were reversed by miR-129 reduction. miR-129 bound to the 3'-untranslated region of TLR4 directly. The NF-κB p65 signaling and NLRP3 inflammasome were abnormally activated after I/R injury, whose impairment after EVs was partially restored by miR-129 downregulation. This study illustrated that EVs could carry miR-129 to mitigate myocardial I/R injury via downregulating TLR4 and disrupting the NF-κB signaling and NLRP3 inflammasome.

Time-resolved Fluorescence Immunoassay (TRFIA) for the Simultaneous Detection of MMP-9 and Lp-PLA2 in Serum.

Currently, atherosclerosis accounts for the majority of cardiovascular morbidity and mortality worldwide, and predicting the stability of atherosclerotic plaque is the main method to prevent atherosclerotic death. This study aims to establish a dual-label time-resolved fluorescence immunoassay (TRFIA) of matrix metalloprotein-9 (MMP-9) and lipoprotein-associated phospholipaseA2 (Lp-PLA2) to predict atherosclerotic plaque stability. A dual-label TRFIA was introduced for the simultaneous quantification of MMP-9 and Lp-PLA2 using fluorescent lanthanide (Eu3+ and Sm3+) chelates. The performance (sensitivity, specificity, accuracy, precision and reference intervals in different subjects) of this TRFIA was evaluated and compared with commercial kit. The sensitivity of the TRFIA for MMP-9 was 0.85 ng/mL and for Lp-PLA2 was 0.68 ng/mL with high affinity and specificity. The average recoveries were 94.58% to 109.82%, and 104.32% to 109.26%, respectively. All intra- and inter-assay CVs ranged from 3.10% to 5.46%. For the normal subjects, the cutoff value was 160.70 ng/mL for MMP-9 and 183.73 ng/mL for LP-PLA2; for the subjects with stable plaque, the cutoff value was 181.98~309.22 ng/mL for MMP-9 and 194.73~337.89 ng/mL for LP-PLA2; for the subjects with unstable plaque, the cutoff value was 330.43 ng/mL for MMP-9 and 343.23 ng/mL for LP-PLA2. This TRFIA detection results agreed well with the results of commercial kit (R2=0.9567 and R2=0.9771, respectively) in clinical serum samples. The TRFIA developed has a wide detection range and good sensitivity for the high-throughput simultaneous detection of MMP-9 and Lp-PLA2 in serum, which provides a new method for predicting the stability of atherosclerotic plaque.

Contribution of peroxisomal docking machinery to mycotoxin biosynthesis, pathogenicity and pexophagy in the plant pathogenic fungus Fusarium graminearum.

Peroxisomal proliferation is highly stimulated during the biosynthesis of mycotoxins and plant infection by Fusarium graminearum. Currently, the functions of the peroxisome in these cellular processes are poorly understood. In this study, we applied genetic, cell biological and biochemical analyses to investigate the functions of the peroxisomes. We constructed targeted deletion of docking machinery components, including FgPex13, FgPex14 and the filamentous fungal specific peroxin FgPex33. Our results indicated that peroxisome dysfunction resulted in a shortage of acetyl-CoA, the precursor of trichothecene biosynthesis, and subsequently decreased deoxynivalenol (DON) production. Deletion mutants of ΔFgPex13, ΔFgPex14 or ΔFgPex33 showed an increased accumulation of endogenous reactive oxygen species (ROS) and reduced phosphorylation of MAP (Mitogen-Activated Protein) kinase FgMgv1. In addition, mutants of the docking peroxin exhibited increased sensitivity toward host oxidative bursts and cell wall integrity stress agents and reduced virulence on host plants. More importantly, we found for the first time that FgPex14 is required for pexophagy in F. graminearum. Overall, our study suggests that peroxisomes play critical roles in DON biosynthesis and virulence in F. graminearum.

The spo0A-sinI-sinR Regulatory Circuit Plays an Essential Role in Biofilm Formation, Nematicidal Activities, and Plant Protection in Bacillus cereus AR156.

The rhizosphere bacterium Bacillus cereus AR156 is capable of forming biofilms, killing nematodes, and protecting plants. However, the underlying molecular mechanisms of these processes are not well understood. In this study, we found that the isogenic mutants ΔBcspo0A and ΔBcsinI have significantly reduced colonization and nematicidal activity in vitro and biological control efficacy on the tomato plant under greenhouse conditions. We further investigated the role of the spo0A-sinI-sinR regulatory circuit in biofilm formation, killing against nematodes, and biological control in AR156. Results from mutagenesis of those regulatory genes in AR156 and their heterologous expression in B. subtilis suggested that the spo0A-sinI-sinR genetic circuit is not only essential for biofilm formation and cell differentiation in AR156 but also able to functionally replace their counterparts in B. subtilis in a nearly indistinguishable fashion. Genome-wide transcriptional profiling in the wild type and the ΔBcspo0A and ΔBcsinI mutants further revealed hundreds of differentially expressed genes, likely positively regulated by both Spo0A and SinI (via SinR) in AR156. Among them, 29 genes are predicted to be directly controlled by SinR, whose counterpart in B. subtilis is a biofilm master repressor. Collectively, our studies demonstrated the essential role of the spo0A-sinI-sinR regulatory circuit in biofilm formation, cell differentiation, and bacteria-host interactions in B. cereus AR156.

Experimental research on the transport-transformation of organic contaminants under the influence of multi-field coupling at a site scale.

Organic-contaminated shallow aquifers have become a global concern of groundwater contamination, yet little is known about the coupled effects of hydrodynamic-thermal-chemical-microbial (HTCM) multi-field on organic contaminant transport and transformation over a short time in aquifers. Therefore, this study proposed a quick and efficient field experimental method for the transport-transformation of contaminants under multi-field coupling to explore the relationship between organic contaminants (total petroleum hydrocarbon (TPH), polycyclic aromatic hydrocarbons (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX) and phthalates acid esters (PAEs)) and multi-field factors. The results showed that hydrodynamics (affecting pH, p < 0.001) and temperature (affecting dissolved oxygen, pH and HCO3-, p < 0.05) mainly affected the organic contaminants indirectly by influencing the hydrochemistry to regulate redox conditions in the aquifer. The main degradation reactions of the petroleum hydrocarbons (TPH, PAHs and BTEX) and PAEs in the aquifer were sulfate reduction and nitrate reduction, respectively. Furthermore, the organic contamination was directly influenced by microbial communities, whose spatial patterns were shaped by the combined effects of the spatial pattern of hydrochemistry (induced by the organic contamination pressure) and other multi-field factors. Overall, our findings imply that the spatiotemporal patterns of organic contaminants are synergistically regulated by HTCM, with distinct mechanisms for petroleum hydrocarbons and PAEs.

Moxibustion alleviates intestinal inflammation in ulcerative colitis rats by modulating long non-coding RNA LOC108352929 and inhibiting Phf11 expression.

Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients with UC and reduce intestinal inflammation in rats with UC. However, it remains unclear whether the ameliorative effect of moxibustion on intestinal mucosal inflammation in UC is related to lncRNAs. Thirty-two rats were randomly assigned to four groups: normal control, UC, moxibustion (MOX), and sulfasalazine (SASP). The UC rat model was induced by administering 4% dextran sulfate sodium (DSS) in drinking water. Rats in the moxibustion group underwent bilateral Tianshu (ST25) moxibustion using the herbs-partition moxibustion method. Rats in the sulfasalazine group received SASP solution via gavage twice daily for seven consecutive days. Our results revealed that, compared with the UC group [2.00 (1.00, 2.50)], the DAI score [0.25 (0.00, 0.50)] was significantly lower in the MOX group (P < 0.05). Compared with the UC group [13.00 (11.25, 14.00)], the histopathological score [5.50 (4.00, 7.75)] was significantly lower in the MOX group (P < 0.05). In addition, the CMDI and macroscopic scores were decreased in the MOX group (P < 0.05). Moxibustion significantly decreased the protein expression of inflammatory factors TNF-α, IFN-γ, and IL-1ß in the colonic tissues of UC rats (P <0.05), thereby suppressing the inflammatory response. Moreover, moxibustion exerted a regulatory influence on colon lncRNA and mRNA expression profiles, upregulating LOC108352929 and downregulating Phf11 in rats with UC (P <0.05). Moxibustion also led to a reduction in the expression and colocalization of Phf11 and NF-κB in the colons of UC rats. Moreover, knockdown of LOC108352929 in rat enteric glial cells demonstrated a significant upregulation of TNF-α mRNA expression (P <0.05). In summary, these data illustrate that moxibustion effectively ameliorates DSS-induced colonic injury and inflammation while exerting regulatory control over the lncRNA-mRNA co-expression network in UC rats. Collectively, the in vivo and in vitro studies suggested that LOC108352929-Phf11 may serve as a potential biological marker for moxibustion in the treatment of UC.

68Ga-FAPI PET/CT Imaging of Intracranial Syphilitic Gumma: Comparison to 18F-FDG PET/CT.

ABSTRACT: Intracranial syphilitic gumma is a rare neurological disease. We present 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT findings of intracranial syphilitic gumma in a 46-year-old man with HIV. In this case, 68Ga-DOTA-FAPI-04 PET/CT outperforms 18F-FDG in helping to visualizing syphilitic gumma. Syphilitic gumma can also cause increase FAPI activity. Our findings suggest the potential value of 68Ga-DOTA-FAPI-04 in the diagnosis of syphilis.

The association of cancer-related fatigue on the social, vocational and healthcare-related dimensions of cancer survivorship.

BACKGROUND: Cancer-related fatigue (CRF) is well documented in cancer survivors, but little is known about the personal and societal impact of CRF. This study aimed to examine the impact of CRF in relation to social and vocational functioning and health care utilization in a large sample of post-treatment cancer survivors. METHODS: We conducted a cross-sectional descriptive study of early stage breast and colorectal cancer survivors (n = 454) who were within 5 years from treatment completion. Social difficulties (SDI-21), work status, absenteeism and presenteeism (WHO-HPQ) and healthcare utilization (HSUQ) were compared in those with (CFR +) and without (CRF -) clinically significant fatigue (FACT-F ≤ 34). RESULTS: A total of 32% met the cut-off criteria for CRF (≤ 34). Participants with CRF + had significantly higher scores on the SDI-21 across all domains and 55% of CRF + vs. 11% in CRF - was above the SDI cut-off (> 10) for significant social difficulties. Participants with CRF + were 2.74 times more likely to be unemployed or on leave (95% CI 1.62, 4.61, p < 0.001). In the subgroup of participants who were currently working (n = 249), those with CRF + reported working on average 27.4 fewer hours in the previous 4 weeks compared to CRF - (p = 0.05), and absolute presenteeism was on average 13% lower in the CRF + group (95% CI 8.0, 18.2, p < 0.001). Finally, individuals with CRF + reported significantly more physician (p < 0.001), other health care professional (p = 0.03) and psychosocial visits (p = 0.002) in the past month. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: CRF is associated with substantial disruption in social and work role functioning in the early transitional phase of cancer survivorship. Better management of persistent CRF and funding for the implementation of existing guidelines and recommended evidence-based interventions are urgently needed.

Effectiveness of different acupuncture therapies for chronic cancer pain: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Pain is a common and distressing symptom experienced by cancer patients. Previous research found acupuncture was associated with significant reductions in pain intensity and opioid use. Acupuncture therapies are various, and the difference in efficacy and safety has never been assessed. This paper aims to assess and rank the effectiveness of the different acupuncture methods and provide an acupuncture treatment guideline for relieving chronic pain in cancer survivors. METHODS: Four English databases (PubMed, Embase, Cochrane library, and Web of Science) and 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Data, and Chinese Biomedical Literature Database) will be searched for randomized controlled trials (RCTs) published from the database inception to November 30, 2021. The primary outcomes will be patient-reported pain intensity measured by the Brief Pain Inventory, Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale, and other valid outcome measures. The Grading of Recommendations Assessment, and Development and Evaluation System will evaluate the quality of evidence. Bayesian network meta-analysis will be performed in WinBUGS V.1.4.3 to determine the comparative effectiveness of the acupuncture therapies. RESULTS: This study will quantify the effectiveness of each acupuncture intervention for chronic cancer pain with pain scores and the use of analgesics. The adverse events of acupuncture treatment for cancer pain will also be reported. CONCLUSION: The conclusion of our study will help physicians and patients choose suitable acupuncture methods to manage cancer pain.

Implementing and Evaluating the Impact of BoneRx: A Healthy Bone Prescription for Men with Prostate Cancer Initiating Androgen Deprivation Therapy.

Background: The initiation of Androgen Deprivation Therapy (ADT) results in rapid and profound hypogonadism, resulting in significant bone and muscle loss, increasing the risk for osteoporosis (OP), falls, and fractures. Despite this, there exist very low rates of guideline adherent care regarding bone health in this population. We developed and implemented a healthy bone prescription tool entitled BoneRx to facilitate the uptake of guideline-concordant bone health care into practice and increase patient awareness and promote the uptake of health bone behaviours (HBBs). Methods: We conducted a cross-sectional pre-BoneRx implementation (n = 143) vs. post-implementation (n = 149) cohort study to evaluate the impact on (i) bone health care, patient engagement in HBB, and patient knowledge and health beliefs regarding OP. Results: There was a significant difference pre- vs. post BoneRx implementation on receipt of baseline BMD (34.7% vs. 59.5%, p < 0.0001) and bone health counselling (32.4% vs. 59.9%, p < 0.0001). More participants in the post-BoneRx implementation cohort reported taking vitamin D supplements 57% vs. 81% (p < 0.001) and calcium supplements 39% vs. 61% (p < 0.001). Physical activity levels also significantly increased (p = 0.021). No differences were detected in OP knowledge or feelings of OP susceptibility, seriousness, or health motivation. Conclusion: BoneRx is a simple, cost-effective, and acceptable strategy that could improve the care of PCa survivors receiving ADT.

Association of Acupuncture and Auricular Acupressure With the Improvement of Sleep Disturbances in Cancer Survivors: A Systematic Review and Meta-Analysis.

Background: Studies on the efficacy of acupuncture and auricular acupressure on sleep disturbances in cancer patients have been growing, but there is no specific and comprehensive systematic review and meta-analysis. This review aims to evaluate the efficacy and safety of acupuncture and auricular acupressure on sleep disturbances in cancer survivors based on existing randomized clinical trials (RCTs). Methods: Four English-language and four Chinese-language biomedical databases were searched for RCTs published from database inception to July 30, 2021. RCTs comparing acupuncture and auricular acupressure with sham control, drug therapy, behavior therapy, or usual care for managing cancer were included. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias (ROB) tool. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for the effect sizes. Results: Thirteen RCTs with 961 patients were included. The risk of performance bias or reporting bias for most of the included trials was high or unclear. Evidence was not found for short-term effects on sleep scales compared to sham control (MD, 1.98; 95% CI, 0.33-3.64; p = 0.02; I2 = 36%), wait list control (MD, 0.40; 95% CI, -0.87-1.68; p = 0.54; I2 = 49%), drug therapy (MD, 1.18; 95% CI, -3.09-5.46; p = 0.59; I2 = 98%). For long-term effect, two sham-controlled RCTs showed no significance of acupuncture on insomnia scale scores (MD, 1.71; 95% CI, -2.38-5.81; p = 0.41; I2 = 89%). Subgroup analyses suggested no evidence that auricular acupressure (MD, 3.14; 95% CI=1.52, 4.76; p = 0.0001; I2 = 0%) or acupuncture (MD, 0.54; 95% CI=-1.27, 2.34; p = 0.56; I2 = 0%) was associated with the reduction in insomnia scale scores. Conclusions: This systematic review and meta-analysis found no evidence about acupuncture or auricular acupressure in the improvement of sleep disturbances in cancer survivors in terms of short- or long-term effect. Adverse events were minor. The finding was inconsistent with previous research and suggested that more well-designed and large-scale randomized controlled trials are needed to identify the efficacy of acupuncture and auricular acupressure for sleep disturbances in cancer survivors. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42020171612.

Can Immune-related adverse events serve as clinical biomarkers of PD-1/PD-L1 inhibitor efficacy in Pan-Cancer Patients?

Although PD-1/PD-L1 inhibitors are widely used as first-line treatment for patients with advanced tumors or as adjuvant therapy for patients with early-stage tumors, their efficacy is only 15-60%. Increasing evidence has demonstrated that biomarkers such as PD-L1 expression levels, microsatellite instability, and tumor mutation burden may assist in predicting the anti-tumor efficacy of PD-1/PD-L1 inhibitors. However, their clinical application value is limited, and there is currently a dearth of specific clinical markers to monitor or predict the efficacy of PD-1/PD-L1 inhibitors. Recently, studies have exposed that the efficacy of PD-1/PD-L1 inhibitors is positively correlated with immune-related adverse events (irAEs), suggesting that the latter may effectively predict anti-tumor efficacy. While there are controversies, a systematic understanding of the reasons and influencing factors of its correlation is still lacking. Therefore, this review aimed to introduce and discuss the latest research on the correlation between the efficacy of PD-1/PD-L1 inhibitors and irAEs. We identified that this positive correlation might be related to adipose tissue, T cells, pharmacokinetic characteristics, and antigen spread. In addition, the severity of irAEs, the duration of the use of PD-1/PD-L1 inhibitors, the comprehensive evaluation method of the severity of irAEs, and the genetic determinants are potentially the most significant bias factors when evaluating this correlation.

Acupuncture combined with traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for chronic insomnia: study protocol for a randomized controlled trial.

INTRODUCTION: The incidence of insomnia is getting higher and higher. Long-term insomnia seriously affects people's health. Drug use is usually accompanied with adverse events. Both acupuncture and cognitive behavioral therapy for insomnia (CBT-I) have been proven to be safe and effective non-pharmacological treatments for insomnia. As the insomniacs' bad sleep behavior and wrong cognition have not been effectively corrected, acupuncture has a quick effect, high patient compliance but unstable long-term efficacy, while CBT-I is complex, time-consuming, and expensive; additionally, patient compliance is low, and the number of trained therapists is limited, making it difficult to carry out. Therefore, this study aims to use the insomnia TCM system to construct a convenient and feasible traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for Chinese people, and combine the advantages of acupuncture and TCM-eCBT-I for maintaining long-term efficacy, and three treatments will be evaluated to provide clinicians with a more effective clinical protocol METHODS AND ANALYSIS: This study is a single-center, open-label, randomized controlled trial. Ninety subjects will be recruited and randomly assigned to three groups: the acupuncture group, the TCM-eCBT-I group, and the acupuncture combined with TCM-eCBT-I group, in a ratio of 1:1:1. We will evaluate the Pittsburgh Sleep Quality Index (PSQI) and Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS), Insomnia Severity Index (ISI), sleep diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 Scale (FS-14) scales. All adverse reactions will be assessed through the ADVERSE event table. All outcomes will be evaluated online at 0 weeks, 4 weeks, 8 weeks, 16 weeks, and 28weeks. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of the Affiliated Hospital of Nanjing University of Chinese Medicine (2020 NL-018-02). Informed consent will be obtained from all the subjects. The results will be shared with sleep researchers, public, and relevant academic institutions through high-impact peer-reviewed publications. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000032960. Registered on 17 May 2020.

Transcutaneous Electrical Acupoint Stimulation for Moderate to Severe Pain in Hepatocellular Carcinoma: A Protocol for a Randomized Controlled Trial.

Background: Cancer-related pain is one of the primary symptoms of patients with hepatocellular carcinoma (HCC). Previous studies have shown that transcutaneous electrical acupoint stimulation (TEAS) is effective in treating patients with acute or chronic pain. In China, it is indispensable to evaluate the efficacy of TEAS in combination with opioids for the treatment of moderate to severe HCC-related pain. Methods/Design: This is a single-center clinical, prospective randomized controlled clinical trial protocol. 104 patients will be randomly divided into the observation group and the control group in a ratio of 1:1.In addition to routine cancer pain medication, the two groups of patients will receive TEAS treatment twice a day for one week. Acupoints will include bilateral Hegu(LI4), Neiguan(PC6), Zusanli(ST36), Taichong(LR3), Ganshu(BL18), Geshu(BL17), Qimen(LR14), and Zhangmen(LR13). The treatment time is from 9:00 a.m. to 11:00 p.m. and from 4:00 p.m. to 6:00 p.m. The primary outcome measures are the Numerical Rating Scale (NRS) and the secondary outcome measures include the Brief Pain Inventory(BPI), dosage and administration duration of opioid drugs, frequency of nausea, vomiting and defecation, Karnofsky Performance Status Scale (KPS), Quality of life scale (QOL), Brief Fatigue Inventory (BFI). The outcome measures will be evaluated at baseline, during treatment and 1 week after treatment. Discussion: Results of this trial are expected to clarify the value of TEAS stimulation performed on specific points in the management of moderate to severe pain in HCC. Trial registration: Chinese clinical trial registry, ChiCTR2100044615 (http://www.chictr.org.cn), Registered on 24 March 2021.

Preparation of acylated blueberry anthocyanins through an enzymatic method in an aqueous/organic phase: effects on their colour stability and pH-response characteristics.

To explore the potential of anthocyanins in pH-colour responsive intelligent packaging and improve the stability of the pigments, 3,4,5-trimethoxybenzoic acid and gallic acid were grafted onto blueberry anthocyanins via enzyme-catalysed grafting. The structural analysis based on UV-vis and IR spectroscopy showed that the two acids were successfully grafted onto the blueberry anthocyanins. The acylation degrees of the 3,4,5-trimethoxybenzoic acid-acylated anthocyanin (Tr-An) and gallic acid-acylated anthocyanin (Ga-An) were 6.38% and 6.51%, respectively. The results from the DPPH radical scavenging assay and ferric reducing antioxidant power assay implied that the antioxidant capacity of Tr-An was worse than that of natural anthocyanin (Na-An), but the antioxidant capacity of Ga-An was stronger than that of Na-An. The grafting of the two acids enhanced the stability of the blueberry anthocyanins and had little effect on the pH-colour response characteristics of the blueberry pigments.