Effects of antibiotic cocktail on the fecal microbiota and their potential correlation of local immune response.

BACKGROUND: The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported. RESULTS: We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria. Extending antibiotic exposure to 2-3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1ß (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001). CONCLUSIONS: Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses.

The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study.

BACKGROUND: Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality. METHODS: We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results. RESULTS: The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002-1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045-1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028-1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001-1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003-1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018-1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression. CONCLUSIONS: In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression.

Urban-rural differences in the prevalence and associated factors of sarcopenia: A systematic review and meta-analysis.

BACKGROUND: Loss of muscle mass, muscle strength, and/or physical performance due to aging is known as sarcopenia. Regardless of how serious this illness is, no single diagnostic criteria have been established. Much research conducted recently has demonstrated differences between built environment characteristics (i.e., urban and rural) and the occurrence of sarcopenia; however, variations in sarcopenia prevalence in urban-rural areas around the world have been reported by fewer studies. This work sought to determine how sarcopenia prevalence varied between urban and rural areas and to explore the associated influencing factors. METHODS: Using the pertinent MESH phrases and free words, PubMed, Web of Science, Embase, and China national knowledge infrastructure databases were scanned for core sarcopenia literature up to February 26, 2023. Observational studies involving urban-rural patients with sarcopenia published in Chinese and English, and assessing muscle mass via computed tomography, bioelectrical impedance, or dual-energy X-ray absorption techniques were considered as inclusion criteria. The meta-analysis involved analysis of the urban-rural prevalence in subgroups by diagnostic criteria, tools for assessing muscle mass and study type, as well as the factors related to urban-rural differences in the occurrence of sarcopenia. STATA version 11.0 was used to perform the statistical analysis. RESULTS: Sixty-six articles involving 433,091 participants were included for analysis: of which 27 were analyzed for both prevalence and related factors whereas 39 were for only prevalence. The meta-analysis revealed the prevalence of sarcopenia to be 0.18 (95 % CI 0.14-0.22), with significant heterogeneity (P < 0.001; I2 = 99.9 %). Moreover, the prevalence of sarcopenia in urban group [0.16 (I2 = 99.9 %, 95 % CI 0.1-0.22)] was lower than in rural group [0.2 (I2 = 99.6 %, 95 % CI 0.16-0.25)] and urban-rural group [0.21 (I2 = 97.5 %, 95 % CI 0.16-0.25)]. Besides, the factors significantly associated with sarcopenia in urban-rural areas were age, gender, BMI, malnutrition, physical activity, and polypharmacy. There was significant heterogeneity between these factors and the association of sarcopenia. CONCLUSIONS: Sarcopenia is associated with aspects of the built environment, and studies have revealed that sarcopenia is more common in rural than in urban populations with influencing factors including age, gender, BMI, poor nutrition, insufficient physical activity, and polypharmacy. The lack of uniform diagnostic criteria makes a robust and comprehensive assessment difficult. Therefore, the formation of certain universal and standardized diagnostic criteria will help future research on sarcopenia.

Association between oxidative balance score and skeletal muscle mass and strength: NHANES from 2011 to 2018.

Objective: Oxidative stress is a risk factor for sarcopenia. The Oxidative Balance Score (OBS) is a widely employed tool for evaluating the oxidative stress-related exposures from dietary and lifestyle factors. In this study, we aimed to conducted to explore the relationship between OBS and skeletal muscle mass and strength. Methods: 6,438 subjects from 2011 to 2018 and 5,414 from 2011 to 2014 from the National Health and Nutrition Examination Survey (NHANES) were selected for analysis. The correlations between OBS and skeletal muscle mass and handgrip strength were investigated using multivariate logistic regression and linear regression analysis. Results: Compared with lowest OBS, participants with OBS in the highest quartile had lower risk of low skeletal muscle mass (OR = 0.173 (0.120 ~ 0.248), p < 0.0001) and low handgrip strength (ß = 0.173 (0.120 ~ 0.248), p = 0.011). The negative association also were found between dietary/lifestyle OBS and skeletal muscle mass (OR = 0.268 (0.178 ~ 0.404), p < 0.0001; OR = 0.231 (0.130 ~ 0.410), p < 0.0001) and handgrip strength (ß = 1.812 (0.555 ~ 3.071), p = 0.008; ß = -2.255 (-3.430 ~ -1.079), p < 0.001) independently. The positive association remains significant, especially among men and those with higher education levels by subgroup analysis. Conclusion: All of these results indicated a negative association between OBS and low skeletal muscle mass and handgrip strength. An antioxidant-rich diet and healthy lifestyle are crucial for enhancing skeletal muscle mass and strength.

Artesunate attenuates serum amyloid A-induced M1 macrophage differentiation through the promotion of PHGDH.

Clinical studies indicated that Serum Amyloid A (SAA) might be a promising biomarker for forecasting the activity, severity, and adverse prognosis of systemic lupus erythematosus (SLE). Simultaneously, a positive correlation has been observed between macrophages, Th17 cells, and SLE disease activity, with both these immune cells being affected by SAA. Presently, the relationship between SAA and the aforementioned immune cell types in SLE remains to be elucidated. To discern the immune cell type most closely associated with SAA, we undertook a single-cell RNA sequencing data analysis via the GEO database. Subsequent results revealed a strong association between macrophages and SAA, a relationship further validated through flow cytometry of spleen macrophages in the MRL/lpr model. We discovered that SAA stimulate M1 macrophage differentiation along with the upregulation of pro-inflammatory cytokines such as IL-6 and IL-1ß. Our findings suggest that SAA may promote M1 macrophage differentiation via the downregulation of phosphoglycerate dehydrogenase (PHGDH). Artesunate (ART), primarily utilized for malaria treatment, was shown to inhibit M1 macrophage differentiation and pro-inflammatory cytokine levels via upregulating the PHGDH expression, thereby attenuating the disease activity in SLE.

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study.

Background: Currently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs. Methods: We retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis. Results: Our results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666-1.283, P IVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (P IVW-FDR-corrected = 0.033) and multivariable MR analysis (P MV-IVW < 0.05), indicating that EPA may be considered as the risk-protecting PUFAs for PsA. Additionally, high levels of LA showed a positive causal relationship with a higher risk of PsA (ORIVW: 1.248, 95% CI: 1.013-1.538, P IVW = 0.037). It is interesting to note, however, that the effects of these associations were weakened in our MVMR analyses, which incorporated adjustment for lipid profiles (P MV-IVW > 0.05) and multiple testing using the FDR method (P IVW-FDR-corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality. Conclusion: Our comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study.

A correlation between mental illness and systemic rheumatoid arthritis (RA) has been observed in several prior investigations. However, little is known about the causative relationship between them. The present study aimed to systematically investigate the potential association between genetically determined mental illness and RA. Two-sample bidirectional Mendelian randomization (MR) analysis was performed using publicly released genome-wide association studies (GWAS). We selected independent genetic variants associated with four mental illnesses (bipolar disorder, broad depression, major depression, and anxiety) as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between mental illness and RA. Results of the IVW analysis suggested that genetic predisposition to bipolar disorder was associated with a decreased risk of RA (odds ratio [OR] = 0.825, 95% CI = 0.716 to 0.95, p = 0.007). Furthermore, we did not find a significant causal effect of RA on bipolar disorder in the reverse MR analysis (p > 0.05). In addition, our study found no evidence of a bidirectional causal relationship between genetically predicted broad depression, major depression, anxiety, and RA (p > 0.05). The genetically proxied bipolar disorder population has a lower RA risk, which may indicate that there is a hidden mechanism for inhibiting the pathogenesis of RA in bipolar disorder. However, results do not support a causal connection between depression, anxiety, and RA.

Potential Targets and Mechanisms of Jiedu Quyu Ziyin Decoction for Treating SLE-GIOP: Based on Network Pharmacology and Molecular Docking.

Background: Systemic lupus erythematosus (SLE) is characterized by poor regulation of the immune response leading to chronic inflammation and multiple organ dysfunction. Glucocorticoid (GC) is currently one of the main treatments. However, a high dose or prolonged use of GC may result in glucocorticoid-induced osteoporosis (GIOP). Jiedu Quyu Ziyin decoction (JP) is effective in treating SLE and previous clinical studies have proved that JP can prevent and treat SLE steroid osteoporosis (SLE-GIOP). We aim to examine JPs main mechanism on SLE-GIOP through network pharmacology and molecular docking. Methods: TCMSP and TCMID databases were used to screen potential active compounds and targets of JP. The SLE-GIOP targets are collected from GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. R software was used to obtain the cross-targets of JP and SLE-GIOP and to perform GO and KEGG enrichment analysis. Cytoscape software was used to make the Chinese Medicines-Active Ingredient-Intersection Targets network diagram. STRING database construct protein-protein interaction network and obtain the core targets. Auto Dock Tools and Pymol software were used for docking. Results: Fifty eight targets overlapped between JP and SLE-GIOP were suggested as potential targets of JP in the treatment of SLE-GIOP. Network topology analysis identified five core targets. GO enrichment analysis was obtained 1,968 items, and the top 10 biological process, closeness centrality, and molecular function were displayed. A total of 154 signaling pathways were obtained by KEGG enrichment analysis, and the top 30 signaling pathways were displayed. JP was well bound by MAPK1, TP53, and MYC according to the molecular docking results. Conclusion: We investigated the potential targets and signaling pathways of JP against SLE-GIOP in this study. It shows that JP is most likely to achieve the purpose of treating SLE-GIOP by promoting the proliferation and differentiation of osteoblasts. A solid theoretical foundation will be provided for the future study of clinical and experimental topics.

In vitro tests to evaluate embryotoxicity and irritation of Chinese herbal medicine (Pentaherbs formulation) for atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder and its prevalence is increasing in the last few decades. No treatment can cure the condition. Pregnancy often worsens the clinical manifestation. There are considerable interests in Chinese Herbal Medicine (CHM) as an alternative treatment for AD. A well tolerated CHM formula (Pentaherbs formulation, PHF) has been proven efficacious in improving life quality and reducing topical corticosteroid use in children with moderate-to-severe AD. However, safety data of PHF are not available. AIM OF THE STUDY: Our study aimed to evaluate the safety of PHF and its 5 individual herbal extracts, including embryotoxicity by Embryonic Stem Cell Test (EST) and irritation by Skin Irritation Test (SIT). MATERIALS AND METHODS: Quality of 5 herbal extracts of PHF was confirmed by chromatography. In EST, mouse embryonic stem cell line (D3) and mouse fibroblast cell line (3T3) were used to study potential embryotoxicity. Three endpoints were assessed by concentration-response curves after 10 days' culture: 50% inhibition of D3 differentiation into beating cardiomyocytes (ID50D3), 50% cytotoxic effects on D3 (IC50D3) and on fibroblasts (IC503T3). A biostatistically based prediction model (PM) was applied to predict the embryotoxic potentials of each CHM. In SIT, epidermis equivalent commercially available kits (EpiDerm™) were used, and concentration-viability curves were obtained by MTT assay to detect skin irritations of each CHM. RESULTS: Chemical authentication confirmed that 5 test herbal extracts contained their main active compounds. EST results indicated that the formula PHF and its individual CHMs were non-embryotoxic, except one CHM, Amur Corktree Bark (Huang Bai, Phellodendron chinense C.K.Schneid), was weakly embryotoxic. SIT results showed that cell viability was above 50% after treatment with different concentrations of all tested CHMs. CONCLUSIONS: Our in vitro tests provided preliminary evidence for safety of the formula PHF in embryonic stem cell test and skin irritation model, but PHF shall be cautiously used in pregnant women with AD. Further studies are needed to support its clinical application as an alternative treatment for AD, especially to the patients who plan for pregnancy or at lactation stages.

Shenhuang Plaster Application Improves Gastrointestinal Motility in Mice with Postoperative Ileus through Intestinal Microbiota.

Postoperative ileus (POI) is a common surgical complication, and its incidence remains high. Shenhuang Plaster (SHP) is a famous traditional Chinese medicine with a definite curative effect on postoperative intestinal dysfunction; however, the mechanisms involved in these effects are unclear. Accordingly, in this study, we constructed a POI mouse model and used the intestinal flora as the target to explore the regulatory effect of SHP on gastrointestinal motility. The results illustrated that SHP applied at the Shenque acupoint promoted the recovery of gastrointestinal motility, relieved intestinal villus atrophy and basal damage caused by POI, protected the integrity of intestinal tissue morphology, and alleviated the inflammatory response in the intestinal tissue of POI model mice. In addition, we clarified the role of the intestinal flora in the occurrence and development of POI, further evaluated the changes in the intestinal flora in each group of mice, and analysed the regulatory effect of SHP on the intestinal flora in mice with POI. The results suggested that SHP might improve gastrointestinal motility disorder in POI mice by effectively regulating intestinal flora.

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis.

Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE. Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16. Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs. Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis.

OBJECTIVE: Recent studies reported that SLE is characterised by altered interactions between the microbiome and immune system. We performed a meta-analysis of publications on this topic. METHODS: Case-control studies that compared patients with SLE and healthy controls (HCs) and determined the diversity of the gut microbiota and the abundance of different microbes were examined. Stata/MP V.16 was used for the meta-analysis. A Bonferroni correction for multiple tests was used to reduce the likelihood of false-positive results. RESULTS: We included 11 case-control studies that examined 373 patients with SLE and 1288 HCs. These studies were performed in five countries and nine cities. Compared with HCs, patients with SLE had gut microbiota with lower Shannon-Wiener diversity index (weighted mean difference=-0.22, 95% CI -0.32 to -0.13, p<0.001) and lower Chao1 richness (standardised mean difference (SMD)=-0.62, 95% CI -1.04 to -0.21, p=0.003). Patients with SLE had lower abundance of Ruminococcaceae (SMD = -0.49, 95% CI -0.84 to -0.15,p=0.005), but greater abundance of Enterobacteriaceae (SMD=0.45, 95% CI 0.01 to 0.89, p=0.045) and Enterococcaceae (SMD=0.53, 95% CI 0.05 to 1.01, p=0.03). However, only the results for Ruminococcaceae passed the Bonferroni correction (p=0.0071). The two groups had no significant differences in Lachnospiraceae and Bacteroides (both p>0.05). Patients with SLE who used high doses of glucocorticoids had altered gut microbiota based on the Chao1 species diversity estimator, and hydroxychloroquine use appeared to reduce the abundance of Enterobacteriaceae. CONCLUSIONS: Patients with SLE have imbalanced gut microbiota, with a decrease in beneficial bacteria and an increase in harmful bacteria. Drugs used to treat SLE may also alter the gut microbiota of these patients.

Shenhuang plaster ameliorates the Inflammation of postoperative ileus through inhibiting PI3K/Akt/NF-κB pathway.

BACKGROUND: Although Shenhuang plaster (SHP) from traditional Chinese medicine prescriptions, has the potential to promote the recovery progression of postoperative ileus (POI), the underlying mechanism remains elusive. Along these lines, in this work, both in vivo and in vitro studies were conducted to systematically explore the regulatory effect and mechanism of SHP on the inflammatory response of the intestinal basal layer in the POI model mice. METHODS: Intestinal manipulation in mice was utilized for the POI model. The impact of SHP in response to POI was evaluated by carrying fluorescein-labeled dextran, histomorphology, immunohistochemistry, in combination with flow cytometry analysis and transcriptome RNA sequencing in vivo. Besides, the cytotoxicity of the SHP treatment on RAW264.7 cells was detected by cell counting kit-8 (CCK-8), the biological effects were assessed by polymerase chain reaction (PCR) and the potential influences on the PI3K/Akt/NF-κB pathway were identified through detecting the expression levels of P85, AKT, IKK and P65 by western blot in vitro. RESULTS: The implementation of the SHP treatment could significantly reduce the expressions of interleukin (IL)- 1ß and tumor necrosis factor (TNF)-α in the intestine, whereas the recovery of gastrointestinal motility is promoted. In addition, SHP can regulate the polarization of macrophages, indicating that the proportion of the M2 type is increased after the application of the SHP treatment. In addition, SHP inhibited the activity of PI3K/AKT/NF-κB signaling pathway-related proteins. CONCLUSION: SHP can significantly ameliorate the inflammatory response of POI and at the same time promote the recovery of gastrointestinal motility. Its mechanism may be mediated by the polarization of macrophages through the PI3K/AKT/NF-κB signaling pathway.

Causal association between rheumatoid arthritis and celiac disease: A bidirectional two-sample mendelian randomization study.

Objectives: Rheumatoid Arthritis (RA) has been associated with Celiac Disease (CD) in previous observational epidemiological studies. However, evidence for this association is limited and inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. This study aimed to assess the bidirectional causal relationship between RA and CD. Methods: In this two-sample Mendelian randomization (MR) study, instrumental variables (IVs) for RA were derived from a genome-wide association studies (GWAS) meta-analysis including 58,284 subjects. Summary statistics for CD originated from a GWAS meta-analysis with 15,283 subjects. The inverse-variance weighted (IVW) method was used as the primary analysis. Four complementary methods were applied, including the weighted-median, weighted mode, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression, to strengthen the effect estimates. Results: Positive causal effects of genetically increased RA risk on CD were derived [IVW odds ratio (OR): 1.46, 95% confidence interval (CI): 1.19-1.79, p = 3.21E-04]. The results of reverse MR analysis demonstrated no significant causal effect of CD on RA (IVW OR: 1.05, 95% CI: 0.91-1.21, p = 0.499). According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. Conclusion: This study reveals a causality of RA on CD but not CD on RA among patients of European descent. This outcome suggests that the features and indicators of CD should regularly be assessed for RA patients.

Moxibustion attenuates inflammation and alleviates axial spondyloarthritis in mice: Possible role of APOE in the inhibition of the Wnt pathway.

Background and aim: Moxibustion is widely used in China and other East Asian countries to manage the symptom of ankylosing spondylitis (AS). This study investigated the effects of moxibustion intervention on protein expression through proteomics analysis in AS mice. Experimental procedure: Proteoglycan-induced spondylitis (PGISp) was established in Balb/c mice. PGISp mice were intervened with daily moxibustion at ST36, BL23, and DU4 for four weeks. Various biochemical (including pro-inflammatory cytokines and bone metabolism indexes) and histopathological parameters were determined. The effects of moxibustion on protein changes in AS mice were analyzed using data-independent acquisition-mass spectrometry (DIA-MS). The target proteins were then confirmed by Western blot analysis. Results: Moxibustion significantly decreased pro-inflammatory cytokine expression including IL-1ß, TNF-α, IL-17, and IL-6, reduced the mRNA expression of RANKL, RANK, ALP, and OCN, and improved the histopathological examination in AS mice. DIA-MS proteomic technique has identified 25 candidate proteins involved in the mechanisms of moxibustion for AS mice, most of which are mainly associated with the regulation of Wnt/ß-catenin. Integrated pathway analysis revealed that glycine, serine and threonine metabolism together with lipid metabolism were the most important canonical pathways involved in the anti-AS effect of moxibustion. In line with the multi-omic data, the levels of BPGM, APOC2, APOE, and GPD1 modified in the AS mice, intervened with moxibustion as confirmed by Western blot. In particular, APOE may play a key role in linking the lipid metabolism and the Wnt/ß-catenin pathway of new bone formation. Conclusion: In conclusion, moxibustion may reduce pro-inflammatory cytokines and improve bone erosion for AS mice. The regulation of APOE by moxibustion may have a potential inhibitory effect on the Wnt/ß-catenin pathway in AS mice. However, due to the lack of silencing or overexpression of key molecules of the signal pathway, whether the beneficial and positive effect of moxibustion involved in the regulation of Wnt/ß-catenin signaling pathway by APOE or other aspects, needed to be explored in further study.

Effects of acupoint massage combined with relaxation therapy on patients with postoperative fatigue syndrome after lumbar surgery.

BACKGROUND: : Lumbar disc herniation (LDH) is a common disease in orthopedics. Surgery is shown to provide significant faster relief of pain compared to conservative therapy. However, due to the influence of surgical trauma, anesthesia and other perioperative stress factors, patients may have complications. Among them, postoperative fatigue syndrome (POFS) is a common complication. Traditional Chinese medicine or integrated traditional Chinese and Western medicine have been proved to be effective in improving postoperative fatigue. METHODS: : This study is a randomized controlled trial. One hundred eighty Chinese patients with POFS of LDH will be randomly divided into control group, experimental group 1, experimental group 2 and experimental group 3 according to the ratio of 1:1:1:1. The patients in the control group will be treated with conventional treatment after operation, the patients in the experimental group 1 will be treated with acupoint massage, the patients in the experimental group 2 will be treated with relaxation therapy, and the patients in the experimental group 3 will be treated with acupoint massage combined with relaxation therapy. The whole treatment will last for 5 days. The main outcome measures will be fatigue visual analogue scale and identity-consequence fatigue scale, and the secondary outcome measures will be hospital anxiety and depression scale. DISCUSSION: : This study is to observe the effects of acupoint massage comblined with relaxation therapy on reducing postoperative fatigue of lumbar disc herniation surgical patients. TRIAL REGISTRATION: : Chinese Clinical Trial Registry (http://www.chictr.org.cn/edit.aspx?pid=123978&htm=4), No. ChiCTR2100044788. Registered on March 27, 2021.

Use of Shenhuang paste on Shenque point improves chemotherapy induced gastrointestinal toxicity in breast cancer: A protocol for randomized controlled trial.

BACKGROUND: Breast cancer, a malignant disorder, occurs in the epithelial tissue of the breast gland. Chemotherapy is the standard treatment for breast cancer, however, the side effect, especially gastrointestinal dysfunction, due to chemotherapy still remain major problems. Traditional Chinese Medicine has been proven therapeutically effective on reducing adverse effects caused by chemotherapy. Shenhuang Plaster. METHODS: The study is a randomized, placebo-controlled, blind trial. A total of 160 Chinese breast cancer patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed Shenhuang plaster application on shenque point (CV8) plus chemotherapy treatment. Patients in the control group will be prescribed placebo plaster application on CV8 plus chemotherapy treatment. The acupoint application will last 3 days. The primary outcome will be the form of faces every day, and the secondary outcomes the symptom score of traditional Chinese medicine, the changes of fecal bacteria and metabolites, serum motilin, gastrin and ghrelin levels. DISCUSSION: This study is to observe therapeutic effects with Shenhuang plaster application on CV8 to regulate chemotherapy-induced gastrointestinal toxicity in breast cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=55262) No. ChiCTR2000034313. Registered on July 2, 2020.

Evidence on Efficacy and Safety of Chinese Medicines Combined Western Medicines Treatment for Breast Cancer With Endocrine Therapy.

BACKGROUND: Breast cancer, a malignant disorder, occurs in epithelial tissue of the breast glands and ducts. Endocrine therapy is commonly applied as an important adjuvant treatment for breast cancer, but it usually induces a variety of side effects. Chinese Medicines (CM) has therapeutic effect on reducing adverse effects of the endocrine therapy in many clinical studies. But strong evidence is still limited on the efficacy and safety of CM combined western medicines (CM-WM) for breast cancer. OBJECTIVE: To study the efficacy and safety of CM-WM as an adjuvant treatment for reducing side effects induced by endocrine therapy in breast cancer patients. METHOD: We searched relevant clinical studies in PubMed and the Chinese National Knowledge Infrastructure (CNKI) databases up to February 28, 2021 and only Randomized Controlled Trials (RCTs) were included. There were no limitations on the languages. We extracted data from the included RCTs, assessed study quality, conducted meta-analyses by RevMan 5.4 and compared the pooled Risk Ratios (RR) or Mean Difference (MD) with 95% CIs. RESULTS: In total 28 trials involving 1,926 participants were included. Six RCTs compared CM-WM with CM placebo-WM, while 22 RCTs compared CM-WM with WM alone. No study compared CM-WM with no treatment. Meta-analysis showed that CM-WM treatment significantly improved quality of life (MD = 0.73, 95% CI = 0.11-1.35, P = 0.02) when compared with CM placebo-WM treatment. When compared with WM treatment alone, CM-WM treatment significantly improved bone mineral density (MD = 0.24, 95% CI = 0.13-0.35, P <0.0001), TCM syndrome score (MD = -5.39, 95% CI = -8.81 to -1.97, P = 0.0002), Kupperman Scale (MD = 0.24, 95% CI = -2.76 to -1.94, P <0.0001), Karnofsky Performance Scale (MD = 3.76, 95% CI = 1.64-5.88, P = 0.0005), quality of life (MD = 3.01, 95% CI = 1.00-5.02, P = 0.003), and pain relief (MD = 2.10, 95% CI = 0.72-3.48, P <0.0001). Compared with WM, CM-WM significantly decreased incidence of TCM symptoms (nausea, vomiting, fatigue, etc.) (RR = 1.60, 95% CI = 1.40-1.84, P <0.0001). For safety, serum calcium, estradiol, ALP, and blood CD3, CD4 and CD8 counts were not significantly difference between two treatments (P >0.05). Serious side effects or reactions were not reported in all included studies. CONCLUSION: The adjunctive use of CM reduced the endocrine therapy associated adverse events, including bone mineral density loss, perimenopausal symptoms, poor quality of life, pain and impaired immune function. But large-scale and high quality RCTs are needed to support the application of CM-WM therapy.

Metabolomic analysis of biochemical changes in the tissue and urine of proteoglycan-induced spondylitis in mice after treatment with moxibustion.

BACKGROUND: Moxibustion is widely used in East Asian countries to manage the symptom of rheumatic diseases. The aim of this study was to identify potential metabolic profiles of moxibustion on relieving ankylosing spondylitis (AS) mice through UHPLC-Q-TOF/MS metabolomic study. METHODS: Thirty-two female Balb/c mice were randomized into healthy control (HC), AS model, moxibustion at acupuncture points (MA) in AS model, and moxibustion at non-acupuncture points (MNA) AS model groups. Moxibustion was administered daily at GV4, bilateral BL23 and bilateral ST36 acupuncture points for four weeks in the MA group. The overall health status, the thickness of hind paws and the tissue concentrations of IL-1ß, PGE2, IL-6 and TNF-α were assessed. The UHPLC-Q-TOF/MS was used to explore the perturbations of endogenous metabolites in tissue and urine of AS model mice intervened by moxibustion. RESULTS: Compared with the AS group, the overall health status was significantly improved after 4-week moxibustion intervention (p < 0.05). The results also showed that MA significantly reduced the levels of paw thickness and decreased the levels of four cytokines in the tissue (p < 0.01). Thirty-seven endogenous metabolites identified by the OPLS-DA were considered to be contributing to therapeutic effects of moxibustion. Moreover, metabolic pathway analysis further revealed that the identified metabolites were mainly involved in TCA cycle, Lipid metabolism, Amino Acid metabolism, Intestinal flora metabolism and Purine metabolism. CONCLUSIONS: UHPLC-Q-TOF/MS based metabolomics approach, as a novel and powerful tool, can help us to gain the insights into potential mechanisms of action of moxibustion for AS.

Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREMτ Expression.

Testicular torsion/detorsion-induced damage is considered as a typical ischemia-reperfusion injury attributed to excessive reactive oxygen species (ROS) production. ROS may regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The cAMP-responsive element modulator-τ (CREMτ) gene expression in the testis is essential for normal germ cell differentiation. The present study was aimed at investigating the effect of sesamol, a powerful antioxidant, on testicular ischemia-reperfusion injury and related mechanisms in an experimental testicular torsion-detorsion rat model. The type of our study was a randomized controlled trial. Sixty rats were randomly divided into the following 3 groups: (1) sham-operated control group (n = 20), (2) testicular ischemia-reperfusion group (n = 20), and (3) testicular ischemia-reperfusion+sesamol-treated group (n = 20). Testicular ischemia-reperfusion was induced by left testicular torsion (720° rotation in a counterclockwise direction) for 2 hours, followed by detorsion. Orchiectomy was performed at 4 hours or 3 months after detorsion. The testis was obtained for the analysis of the following parameters, including malondialdehyde level (a sensitive indicator of ROS), CREMτ expression, and spermatogenesis. In the testicular ischemia-reperfusion group, the malondialdehyde level was significantly increased with a concomitant significant decrease in CREMτ expression and spermatogenesis in ipsilateral testis. These results suggest that overproduction of ROS after testicular ischemia-reperfusion may downregulate CREMτ expression, which causes spermatogenic injury. Sesamol treatment resulted in a significant reduction in the malondialdehyde level and significant increase in CREMτ expression and spermatogenesis in ipsilateral testis. These data support the above suggestion. Our study shows that sesamol can attenuate testicular ischemia-reperfusion injury through scavenging ROS and upregulating CREMτ expression.