Lysophosphatidic acid promotes ESCC progression by increasing the level of CCL2 secreted by esophageal epithelial cells.

BACKGROUND: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA1-LPA6). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain. METHODS: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells. RESULTS: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA1/3, ultimately causing an increase in CCL2 expression and secretion in Het-1a. CONCLUSIONS: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator.

Combined radiofrequency ablation or microwave ablation with transarterial chemoembolization can increase efficiency in intermediate-stage hepatocellular carcinoma without more complication: a systematic review and meta-analysis.

OBJECTIVES: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely used in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) in clinical practice. We aim to compare the efficacy and safety of TACE combined with RFA or MWA versus TACE monotherapy for intermediate-stage HCC. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The outcomes included overall survival (OS), progression-free survival (PFS), local tumor control (LTC) rate, and major complication. Subgroup analysis for different TACE combination therapies was performed. RESULTS: Ten studies with 1799 patients with intermediate-stage HCC were included. The pooled hazard ratio (HR) for OS was in favor of TACE combination therapy (HR, 0.50, 95% confidence interval [CI], 0.40-0.62). Specifically, the TACE combination therapy was associated with higher 1-, 3-, and 5-year OS rates. Regarding tumor progression, the TACE combination therapy showed significantly better PFS (HR, 0.47, 95% CI, 0.37-0.61) and higher 1-, 2- and 3-year PFS rates than TACE monotherapy. The pooled odds ratio (OR) for the LTC was also in favor of TACE combination therapy (OR, 0.36, 95% CI, 0.24-0.53). No significant difference was found between the two groups regarding the major complication rate (OR, 1.26, 95% CI, 0.74-2.16). These results were consistent across subgroups of TACE + RFA versus TACE and TACE + MWA versus TACE. CONCLUSION: TACE combined with RFA or MWA can provide significantly better OS, PFS and LTC than TACE monotherapy for patients with intermediate-stage HCC, without increasing the risk of major complications.

Gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase can predict progression in patients with liver cirrhosis.

OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced biliary imaging from the hepatobiliary phase in predicting hepatic decompensation and insufficiency for patients with cirrhosis. METHODS: This single-center retrospective study included 270 patients who underwent Gd-BOPTA-enhanced magnetic resonance imaging. The relative enhancement ratios of the biliary system (REB) and liver parenchyma (REL) in patients with normal liver function without underlying chronic liver disease and three groups of patients with Child-Pugh A, Child-Pugh B, and Child-Pugh C disease were measured. After a mean follow-up of 38.5 ± 22.5 months, prognostic factors were evaluated using the Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve analyses were performed to assess the capacity of the REB and REL to predict the development of hepatic decompensation and insufficiency. RESULTS: During the follow-up period, nine of 79 patients with Child-Pugh A disease developed hepatic decompensation. The REB was a significant predictive factor (hazard ratio (HR) = 0.40 (0.19-0.84); p = 0.016), but the REL showed no association with hepatic decompensation. Moreover, the areas under the ROC curves (AUCs) were 0.83 and 0.52 for the REB and REL, respectively. Thirty-eight of 207 patients with cirrhosis developed hepatic insufficiency. The REB was a significant predictive factor (HR = 0.24 (0.13-0.46); p < 0.0001), but the REL did not show statistically significant association with hepatic insufficiency. The AUCs were 0.82 and 0.57 for the REB and REL, respectively. CONCLUSIONS: Gd-BOPTA-enhanced biliary imaging from the hepatobiliary phase was valuable in predicting hepatic decompensation and insufficiency for cirrhotic patients. KEY POINTS: • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic decompensation in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic insufficiency in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging showed superior predictive values for adverse clinical outcomes compared to liver parenchymal imaging at the hepatobiliary phase.

Integrated analysis of co-expression and ceRNA network identifies five lncRNAs as prognostic markers for breast cancer.

Long non-coding RNAs (lncRNAs), which competitively bind miRNAs to regulate target mRNA expression in the competing endogenous RNAs (ceRNAs) network, have attracted increasing attention in breast cancer research. We aim to find more effective therapeutic targets and prognostic markers for breast cancer. LncRNA, mRNA and miRNA expression profiles of breast cancer were downloaded from TCGA database. We screened the top 5000 lncRNAs, top 5000 mRNAs and all miRNAs to perform weighted gene co-expression network analysis. The correlation between modules and clinical information of breast cancer was identified by Pearson's correlation coefficient. Based on the most relevant modules, we constructed a ceRNA network of breast cancer. Additionally, the standard Kaplan-Meier univariate curve analysis was adopted to identify the prognosis of lncRNAs. Ultimately, a total of 23 and 5 modules were generated in the lncRNAs/mRNAs and miRNAs co-expression network, respectively. According to the Green module of lncRNAs/mRNAs and Blue module of miRNAs, our constructed ceRNA network consisted of 52 lncRNAs, 17miRNAs and 79 mRNAs. Through survival analysis, 5 lncRNAs (AL117190.1, COL4A2-AS1, LINC00184, MEG3 and MIR22HG) were identified as crucial prognostic factors for patients with breast cancer. Taken together, we have identified five novel lncRNAs related to prognosis of breast cancer. Our study has contributed to the deeper understanding of the molecular mechanism of breast cancer and provided novel insights into the use of breast cancer drugs and prognosis.

Efficacy and acceptability of neoadjuvant endocrine therapy in patients with hormone receptor-positive breast cancer: A network meta-analysis.

BACKGROUND: The optimal sequence of endocrine therapy in a neoadjuvant setting for hormone receptor-positive (HR+) breast cancer is unclear. Our study evaluated the efficacy and acceptability of neoadjuvant endocrine therapy for HR+ breast cancer. METHODS: We identified studies based on titles and abstracts that were published before 22 June 2018 in the following databases: PubMed, EMBASE, and the Cochrane Library. Eligible studies were randomised controlled trials with at least one arm that evaluated the effectiveness of one or a combination of anastrozole, letrozole, palbociclib, tamoxifen, fulvestrant, abemaciclib, everolimus, gefitinib, ribociclib, taselisib, and exemestane. We pooled effect sizes using the odds ratio (OR) and corresponding 95% credibility interval (95% CrI). The primary outcomes were response rate and treatment completion. RESULTS: Our network meta-analysis included 3,306 participants and 16 eligible studies, which assessed 15 treatments. In terms of response rates, compared with letrozole combined therapy, tamoxifen was associated with a significant reduction in response rate (OR, 0.34; 95% CrI, 0.13-0.85; OR, 0.32; 95% CrI, 0.13-0.80; OR, 0.26; 95% CrI, 0.09-0.83; and OR, 0.30; 95% CrI, 0.09-0.96; for letrozole plus everolimus, letrozole plus taselisib, letrozole plus zoledronic acid, and letrozole plus lapatinib, respectively). Based on the surface under the cumulative ranking curves ranking, letrozole plus zoledronic acid was associated with the highest rate of response (87.6%), followed by letrozole plus lapatinib (85.2%), and letrozole plus taselisib (79.3%). CONCLUSIONS: Ultimately, our study established that letrozole plus zoledronic acid may be an optimal treatment based on its current rank in a neoadjuvant setting for HR+ breast cancer.

Four lncRNAs associated with breast cancer prognosis identified by coexpression network analysis.

Previous studies on long noncoding RNA (lncRNA) have made breakthroughs in the treatment of several tumors, and these findings have brought attention to the lncRNA signature of breast cancer. Increased understanding of genomic architecture and achievement of innovative therapeutic strategies has prompted creation of a novel oncological model for the treatment of solid cancers. In this study, we systematically analyzed the transcriptome of breast cancer tissues to gain more in-depth knowledge of tumor biology. Gene coexpression relationships were studied in 206 samples from The Cancer Genome Atlas database, and nine coexpression modules were identified. After screening and analysis, we identified four important prognosis-related lncRNAs (HOTAIR, SNHG16, HCP5, and TINCR), and constructed a prognostic model, one (HCP5) of which has not previously been identified in the context of breast cancer. Importantly, an understanding of prognosis facilitates precise disease risk assessment and advances the selection of strategies for risk-adaptive management. These findings broaden the landscape of carcinogenic lncRNAs in breast cancer, providing insights into the biological significance and clinical application of lncRNAs in breast cancer.

The effect of long noncoding RNAs HOX transcript antisense intergenic RNA single-nucleotide polymorphisms on breast cancer, cervical cancer, and ovarian cancer susceptibility: A meta-analysis.

Recent studies have shown that long noncoding RNAs (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) polymorphisms are associated with cancer susceptibility. The greatest threat to women's health among a variety of cancers is breast cancer (BC), cervical cancer (CC), and ovarian cancer (OC), and the incidence of it is increasing. We performed a meta-analysis to clarify the relationship between lncRNA HOTAIR expression and BC, CC, and OC susceptibility. We thoroughly searched PubMed, Embase, and the Cochrane Library to obtain the relevant literature. We extracted data from case groups and control groups for each single-nucleotide polymorphism (SNP) (rs4759314, rs920778, rs189663, rs12826786, rs7958904, and rs874945) and compared the relationship between alleles, codominance models, dominant and invisible models and BC, CC, and OC susceptibility. Our study included 11 studies with a total of 5322 patients. There was a significant association between the rs4759314 polymorphism of HOTAIR and susceptibility to BC, CC, and OC (codominant model: AG/AA odds ratio [OR] = 1.13 [95% confidence intervals [CI], 1.00-1.29], GG/AA OR = 1.54 [95% CI, 1.06-2.23]; dominant model: GG + AG/AA OR = 1.16 [95% CI, 1.02-1.32]; and recessive model: GG/AA + AG OR = 1.51 [95% CI, 1.05-2.19]). The association between the expression of rs920778 and BC, CC, and OC susceptibility was not clear (alleles T/C: OR = 1.28 [95% CI, 0.87-1.89]; in codominant model: CT/CC OR = 1.10, [95% CI, 0.71-1.71], TT/CC OR = 1.29 [95% CI, 0.59-2.80]; dominant model: TC + TT/CC OR = 1.16, [95% CI, 0.73-1.86]; and recessive model: TT/TC + CC OR = 1.43, [95% CI, 0.83-2.47]). HOTAIR polymorphism rs1899663 was associated with BC, CC, and OC susceptibility to a certain extent, (alleles T/G OR = 0.90 [95% CI, 0.69-1.16]; in the codominant model: GT/GG OR = 0.81 [95% CI, 0.50-1.30], TT/GG OR = 1.04 [95% CI, 0.63-1.72]; dominant model: GT + TT/GG OR = 0.82 [95% CI, 0.52-1.29]; and recessive model: TT/GT + GG OR = 1.21 [95% CI, 0.76-1.94]). The rs12826786, rs7958904, and rs874945 polymorphisms were associated with a certain degree of BC, CC, and OC susceptibility, but they were not statistically significant. HOTAIR rs4759314 increased susceptibility to BC, CC, and OC in some patients; rs029778 and rs1899663 also increased susceptibility to some extent. SNPs rs12826786, rs7958904, and rs874945 did not correlate with an effect on patient susceptibility to BC, CC, and OC.

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets.

BACKGROUND: With the development in research, the importance of microRNAs (miRNAs) in the occurrence and metastasis, and prognosis of lung squamous cell carcinoma (LUSC) have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics. MATERIALS AND METHODS: We downloaded miRNA and messenger RNA samples related to LUSC from The Cancer Genome Atlas (TCGA) database. Following initial data screening and preprocessing, we utilized the R platform and a range of analysis tools (miRDB, TargetScanHuman7.2, DAVID, and Cytoscape_v3.5.1) to analyze the TCGA data and identify highly specific and sensitive biomarkers. RESULTS: We finally identified 12 miRNAs and six central genes closely related to the overall survival of patients with LUSC. We found that high expression of 7 miRNAs (miR-301b, miR-383, miR-512, miR-515, miR-525, miR-577, and miR-5682) and low expression of five miRNAs (miR-448, miR-486, miR-4732,miR-4732, miR-516, and miR-1911) can significantly improve the overall survival rate of patients with LUSC. The six central genes DLGAP5, CENPA, CHEK1, LRRK2, CALB1, and TOP2A are directly or indirectly involved in the formation and metastasis of LUSC and could, therefore, be considered as target genes for drug therapy. CONCLUSION: With the development in research, the importance of miRNAs in the occurrence and metastasis and prognosis of LUSC have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics.

Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co-expression network.

PURPOSE: Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC. METHODS: Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan-Meier analysis was used to predict prognosis-related target genes to identify prognostic biomarkers. RESULTS: A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis. CONCLUSION: We performed a distinctive correlation analysis of miRNA-mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.

Comparative effects of 3,4-dimethylpyrazole phosphate (DMPP) and dicyandiamide (DCD) on ammonia-oxidizing bacteria and archaea in a vegetable soil.

Nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and dicyandiamide (DCD) have been used extensively to improve nitrogen fertilizer utilization in farmland. However, their comparative effects on ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in agricultural soils are still unclear. Here, we compared the impacts of these two inhibitors on soil nitrification, AOA and AOB abundance as well as their community structure in a vegetable soil by using real-time PCR and terminal restriction fragment length polymorphism (T-RFLP). Our results showed that urea application significantly increased the net nitrification rates, but were significantly inhibited by both NIs, and the inhibitory effect of DMPP was significantly greater than that of DCD. AOB growth was more greatly inhibited by DMPP than by DCD, and the net nitrification rate was significantly related to AOB abundance, but not to AOA abundance. Application of urea and NIs to soil did not change the diversity of the AOA community, with the T-RFs remaining in proportions that were similar to control soils, while the community structure of AOB exhibited obvious shifts within all different treatments compared to the control. Phylogenetic analysis showed that all AOA sequences fell within group 1.1a and group 1.1b, and the AOB community consisted of Nitrosospira cluster 3, cluster 0, and unidentified species. These results suggest that DMPP exhibited a stronger inhibitory effect on nitrification than DCD by inhibiting AOB rather than AOA.

Age- and gender-related dispersion of brain networks across the lifespan.

The effects of age and gender on large-scale resting-state networks (RSNs) reflecting within- and between-network connectivity in the healthy brain remain unclear. This study investigated how age and gender influence the brain network roles and topological properties underlying the ageing process. Ten RSNs were constructed based on 998 participants from the REST-meta-MDD cohort. Multivariate linear regression analysis was used to examine the independent and interactive influences of age and gender on large-scale RSNs and their topological properties. A support vector regression model integrating whole-brain network features was used to predict brain age across the lifespan and cognitive decline in an Alzheimer's disease spectrum (ADS) sample. Differential effects of age and gender on brain network roles were demonstrated across the lifespan. Specifically, cingulo-opercular, auditory, and visual (VIS) networks showed more incohesive features reflected by decreased intra-network connectivity with ageing. Further, females displayed distinctive brain network trajectory patterns in middle-early age, showing enhanced network connectivity within the fronto-parietal network (FPN) and salience network (SAN) and weakened network connectivity between the FPN-somatomotor, FPN-VIS, and SAN-VIS networks. Age - but not gender - induced widespread decrease in topological properties of brain networks. Importantly, these differential network features predicted brain age and cognitive impairment in the ADS sample. By showing that age and gender exert specific dispersion of dynamic network roles and trajectories across the lifespan, this study has expanded our understanding of age- and gender-related brain changes with ageing. Moreover, the findings may be useful for detecting early-stage dementia.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Occipital connectivity networks mediate the neural effects of childhood maltreatment on depressive symptoms in major depressive disorder.

BACKGROUND: Childhood maltreatment (CM) is a well-established risk factor for major depressive disorder (MDD). The neural mechanisms linking childhood maltreatment experiences to changes in brain functional networks and the onset of depression are not fully understood. METHODS: In this study, we enrolled 66 patients with MDD and 31 healthy controls who underwent resting-state fMRI scans and neuropsychological assessments. We employed multivariate linear regression to examine the neural associations of CM and depression, specifically focusing on the bilateral occipital functional connectivity (OFC) networks relevant to MDD. Subsequently, a two-step mediation analysis was conducted to assess whether the OFC network mediated the relationship between CM experiences and the severity of depression. RESULTS: Our study showed that patients with MDD exhibited reduced OFC strength, particularly in the occipito-temporal, parietal, and premotor regions. These reductions were negatively correlated with CM scores and the severity of depression. Notably, the overlapping regions in the bilateral OFC networks, affected by both CM experiences and depressive severity, were primarily observed in the bilateral cuneus, left angular and calcarine, as well as the right middle frontal cortex and superior parietal cortex. Furthermore, the altered strengths of the OFC networks were identified as positive mediators of the impact of CM history on depression symptoms in patients with MDD. CONCLUSION: We have demonstrated that early exposure to CM may increase vulnerability to depression by influencing the brain's network. These findings provide new insights into understanding the pathological mechanism underlying depressive symptoms induced by CM.

The impact of expectancy on the efficacy of acupuncture treatment for postprandial distress syndrome: Secondary analysis of a randomized clinical trial.

BACKGROUND: Expectancy is an important source of the placebo effect. However, it is unclear whether this has an effect on the efficacy of acupuncture and sham acupuncture in the treatment of postprandial distress syndrome (PDS). AIM: To evaluate the effects of high expectancy (HE) and low expectancy (LE) on the efficacy of acupuncture and sham acupuncture in the treatment of PDS. METHODS: This post hoc secondary analysis used data from our previous randomized controlled trial. Patients were, respectively, enrolled in the HE group and LE group according to expectancy assessments. The composite primary outcomes were the response rate and the elimination rate after 4 weeks of treatment. Expectancy was considered a factor affecting the efficacy of acupuncture treatment only if both primary outcomes achieved significance. RESULTS: For the acupuncture group, the response rate was 84.5% in the HE group and 78.8% in the LE group (p = 0.458), and the elimination rate was 32.1% in the HE group and 21.2% in the LE group (p = 0.241). For the sham acupuncture group, the response rate at week 4 was 52.3% in the HE group and 53.1% in the LE group (p = 0.936), and the elimination rate at week 4 was 23.1% in the HE group and 10.6% in the LE group (p = 0.090). CONCLUSION: In this study, the response rate and elimination rate were higher in the high-expectancy group, but no conclusive evidence was found for an association between expectancy and the efficacy of acupuncture and sham acupuncture.

Platelet-Derived Amyloid-ß Protein Precursor as a Biomarker of Alzheimer's Disease.

BACKGROUND: Platelet proteins may be associated with Alzheimer's disease (AD) pathology. OBJECTIVE: To investigate the relationship between platelet proteins and cerebrospinal fluid (CSF) biomarkers of AD and cognition in individuals with memory decline to identify effective screening methods for detecting the early stages of the disease. METHODS: We classified 68 participants with subjective memory decline according to the ATN framework determined by CSF amyloid-ß (A), CSF p-tau (T), and t-tau (N). All participants underwent Mini-Mental State Examination (MMSE) and platelet-related protein content testing. RESULTS: Eighteen participants had normal AD biomarkers (NCs), 24 subjects had non-AD pathologic changes (non-AD), and 26 subjects fell within the Alzheimer's continuum (AD). The platelet amyloid-ß protein precursor (AßPP) ratio in the AD group was significantly lower than in the non-AD and NCs groups, and positively correlated with MMSE scores and CSF amyloid-ß42 level, which could affect MMSE scores through CSF amyloid-ß42. Levels of platelet phosphorylated-tau 231 and ser396/404 phosphorylated tau were elevated in both AD and non-AD compared to NCs. Additionally, the receiver operating characteristic analysis demonstrated that the platelet AßPP ratio was a sensitive identifier for differentiating the AD from NCs (AUC = 0.846) and non-AD (AUC = 0.768). And ser396/404 phosphorylated tau could distinguish AD from NCs. CONCLUSION: Our study was the first to find an association between platelet AßPP ratio and CSF biomarkers of AD, which contribute to the understanding of the peripheral changes in AD. These findings may help to discover potential feasible and effective screening tools for AD.

[Research progress of acupuncture for peripheral inflammatory response].

Acupuncture can regulate peripheral inflammatory response mainly through somatosensory-vagal/sympathetic nerve-splenic/adrenal/local reflex pathway. Besides, acupuncture may also play an anti-inflammatory role through gut microbiota and neuro-endocrine pathway. The effects of acupuncture have acupoint specificity and time window effect, and are influenced by voltage, current and frequency of electroacupuncture. Future research should focus on the connection and interaction of multiple targets, pathways and mechanisms in the brain, and clarify the multi-target advantages of acupuncture anti-inflammatory.

[Research progress on mechanism of acupuncture and moxibustion in treatment of irritable bowel syndrome].

The current clinical evidence and underlying mechanisms of acupuncture and moxibustion in the treatment of irritable bowel syndrome (IBS) were summarized, so as to better optimize clinical treatment. The relevant articles of acupuncture and moxibustion in the treatment of IBS in recent years were retrieved and summarized. We found that the clinical efficacy of acupuncture and moxibustion in the treatment of IBS was relatively reliable. However, the mutual relationships among various mechanisms of action such as abnormal gastrointestinal motility, high visceral sensitivity, intestinal microenvironment disorders, and abnormal intestinal-brain interactions need to be further explored. The authors believe that in-depth explorations of the bidirectional regulation of "gut-brain axis", the law of changes in the abundance and diversity of intestinal flora, and the establishment of a more ideal animal model of TCM syndrome differentiation are useful ideas for subsequent research.

The Influence of Psychological Status on Acupuncture for Postprandial Distress Syndrome: A Subgroup Analysis of a Multicenter, Randomized Controlled Trial.

BACKGROUND: Postprandial distress syndrome (PDS) is accompanied by a high incidence of mood disorder. Acupuncture is an effective method in relieving dyspepsia symptoms; however, the impact of psychological status on acupuncture for PDS remains mysterious. METHODS: This secondary analysis of a multicenter, randomized controlled trial aims to evaluate the influence of anxiety and depression on acupuncture for PDS. 138 patients received the same acupuncture treatment and were followed up until week 16. The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms after 4 weeks of treatment. RESULTS: Of 114 patients, 31 were anxiety patients and 83 were nonanxiety patients or 32 were depressive patients and 82 were nondepressive patients. The response rate and elimination rate at week 4 were 77.4% and 9.7% in anxiety patients versus 84.3% and 27.7% in nonanxiety patients, respectively (P = 0.388; P = 0.041). No significant difference was noted in the response rate (P = 0.552) and elimination rate (P = 0.254) at week 4 between nondepressive and depressive patients. There was no significant intergroup difference in the response rate and elimination rate between non-mood-disorder and mood disorder patients (P > 0.05) during the 12-week post-treatment follow-up, except for the response rate at week 8 (P < 0.05). CONCLUSION: The effect of acupuncture on response rate was similar for both non-mood-disorder and mood disorder patients. However, anxiety but not depression had a negative influence on the elimination rate, especially in postprandial fullness.

Is acupuncture effective for knee osteoarthritis? A protocol for a systematic review and meta-analysis.

INTRODUCTION: Knee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of acupuncture for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of acupuncture for treating KOA. METHODS AND ANALYSIS: Four English databases (PubMed, Embase, Cochrane Library databases and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Wanfang) will be searched from the database inception to 1 September 2021. All randomised controlled trials related to acupuncture for KOA will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be pain intensity. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The strength of recommendations and quality of evidence will be assessed using the Grading of Recommendations Assessment Development and Evaluation working group methodology. ETHICS AND DISSEMINATION: Ethics approval is not required because individual patient data are not included. This protocol was registered in the international Prospective Register of Systematic Reviews on 25 February 2021. The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal. The findings will also be disseminated through conference presentations. TRIAL REGISTRATION NUMBER: CRD42021232177.

Effects of Electroacupuncture at Different Acupoints on Functional Dyspepsia Rats.

Although, acupoint specificity is regarded as the core of scientific issues in electroacupuncture (EA), the difference of EA on treating functional dyspepsia (FD) at different acupoints is unclear. Therefore, this study aims to investigate the different therapeutic effects of EA at lower extremity or abdominal acupoints on the mucosal integrity and lower-inflammatory response in FD. The intragastric administration of iodoacetamide (IA) was performed in 48 rats to establish the FD model. These rats were randomly divided into the control group, the model group and the six EA groups receiving stimulation at the lower extremity (ST36, ST37, and ST39) or abdominal acupoints (ST25, CV4, and CV12) separately. The open-field test (OFT) was measured after 8 weeks of IA, and gastric emptying was evaluated after 10 days of the EA treatment. The local inflammation markers of CD45, eosinophil major basic protein (EMBP), and the tight junction proteins ZO1 and Claudin3 were assessed by immunofluorescence in all groups. Western blot analysis showed that the EMBP and Occludin1 levels in the duodenal. EA at lower extremity acupoint ST36 could improve the gastric emptying. EA at lower extremity acupoints reduced the immunoreactivity of EMBP, but the CD45 was reregulated by the ST37 and ST39 acupoints. The lower extremity acupoints also ameliorated FD-tight junction protein in the expression of Claudin3 and ZO1. However, only the ST36 suppressed the expression of EMBP and recovered the expression of Occludin1. Similarly, the effect of EA at abdominal acupoints was not obvious either in facilitating gastric motility or in improving inflammatory and mucosal injury. EA at lower extremity and abdominal acupoints with the same stimulation parameters had different therapeutic effects in gastric emptying, intestinal mucosal integrity, and inflammation response, thus proving the specificity of acupoints.