Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.

Age-, season- and gender-specific reference intervals of serum 25-hydroxyvitamin D3 for healthy children (0 ~ 18 years old) in Nanning area of China.

Establishing specific reference intervals (RIs) of serum 25-hydroxyvitamin D3 [25(OH)D] for children is essential for improving the accuracy of diagnosis and prognosis monitoring of diseases such as rickets and growth retardation. The study including 6,627 healthy children was conducted to establish specific RIs of 25(OH)D for children in Nanning area of China. The results showed that there were statistically significant differences among age, season, and gender of serum 25(OH)D levels, and the age-specific RIs of serum 25(OH)D were 20.3 ~ 53.6 ng/mL for 0 ~ ≤ 1 year and 18.9 ~ 49.6 ng/mL for 2 ~ ≤ 3 years. The age-, season-specific RIs of serum 25(OH)D for 4 ~ ≤ 6 years in spring-summer and autumn-winter were 15.8 ~ 42.6 ng/mL and 15.2 ~ 37.7 ng/mL, respectively. The age-, gender-specific RIs of serum 25(OH)D for 7 ~ ≤ 18 years for males and females were 12.1 ~ 36.1 ng/mL and 10.8 ~ 35.3 ng/mL, respectively. This study successfully established the RIs of serum 25(OH)D, which may help to improve disease diagnosis and monitoring for children in the Nanning area of China.

Combined ATAC-seq, RNA-seq, and GWAS analysis reveals glycogen metabolism regulatory network in Jinjiang oyster ( Crassostrea ariakensis).

Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters. The Jinjiang oyster ( Crassostrea ariakensis) is an economically and ecologically important species in China. In the present study, RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents. Analysis identified 9 483 differentially expressed genes (DEGs) and 7 215 genes with significantly differential chromatin accessibility (DCAGs) were obtained, with an overlap of 2 600 genes between them. Notably, a significant proportion of these genes were enriched in pathways related to glycogen metabolism, including "Glycogen metabolic process" and "Starch and sucrose metabolism". In addition, genome-wide association study (GWAS) identified 526 single nucleotide polymorphism (SNP) loci associated with glycogen content. These loci corresponded to 241 genes, 63 of which were categorized as both DEGs and DCAGs. This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C. ariakensis.

The possible impact of the universal two-child policy on pregnancy outcomes.

PURPOSE: The implementation of the universal two-child policy contributes to adverse pregnancy outcomes, but how the policy change leads to adverse pregnancy outcomes is not well elaborated. In this study, we aimed to compare maternal characteristics and complications, accessed the change in the proportion of maternal characteristics and maternal complications, and evaluated the mediation of maternal characteristics on maternal complications. METHODS: Demographic and clinical data of three-level sample facilities were extracted from China's National Maternity Near Miss Obstetrics Surveillance System from Jan 1, 2012 to May 31, 2021. The associations between the universal two-child policy and maternal risk factors, the universal two-child policy and maternal complications, and maternal risk factors and maternal complications were evaluated using multivariate logistic regression analyses, with odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis was used to estimate the potential mediation effects on the associations between the policy and maternal complications. Population-attributable fractions (PAF) were conducted to quantify the maternal complications burden attributable to the implementation of the universal two-child policy. RESULTS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facilities. After adjusting for covariables, there were significant associations between the universal two-child policy and maternal risk factors (P < 0.001), the universal two-child policy and an increased risk of maternal complications (P < 0.001), and maternal risk factors and maternal complications(P < 0.001). The effects of the universal two-child policy on maternal near miss and medical disease were significantly mediated by maternal risk factors with mediation proportions of 19.77% and 4.07% at the municipal-level sample facility, and mediation proportions for 2.72% at the county-level sample facility on medical disease. The universal two-child policy contributed 19.34%, 5.82%, 8.29%, and 46.19% in the incidence of the maternal near miss, antepartum or intrapartum complication, post-partum complication, and medical disease at municipal-level sample facility, respectively. The corresponding PAF% at county-level sample facility was 40.49% for maternal near miss, 32.39% for the antepartum or intrapartum complication, 61.44% for post-partum complication, and 77.72% for medical disease. For provincial-level sample facility, the incidence of maternal near miss, antepartum or intrapartum complications, and medical diseases decreased (P < 0.05) and no statistically significant difference occurred in the incidence of post-partum complications. CONCLUSIONS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facility. Maternal risk factors may play a mediating role in the effect of policy change and maternal complications. Provincial hospitals have been able to improve the quality of perinatal health care and reduce adverse pregnancy outcomes by adjusting their obstetric service strategies in the context of the new birth policy.

Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy.

TJP1, an adaptor protein of the adhesive barrier, has been found to exhibit distinct oncogenic or tumor suppressor functions in a cell-type dependent manner. However, the role of TJP1 in kidney renal clear cell carcinoma (KIRC) remains to be explored. The results showed a marked down-regulation of TJP1 in KIRC tissues compared to normal tissues. Low expression of TJP1 was significantly associated with high grade and poor prognosis in KIRC. Autophagosome aggregation and LC3 II conversion demonstrated that TJP1 may induce autophagy signaling in 786-O and OS-RC-2 cells. Knockdown of TJP1 led to a decrease in the expression of autophagy-related genes, such as BECN1, ATG3, and ATG7. Consistently, TJP1 expression showed a significant positive correlation with these autophagy-related genes in KIRC patients. Furthermore, the overall survival analysis of KIRC patients based on the expression of autophagy-related genes revealed that most of these genes were associated with a good prognosis. TJP1 overexpression significantly suppressed cell proliferation and tumor growth in 786-O cells, whereas the addition of an autophagy inhibitor diminished its inhibitory function. Taken together, these results suggest that TJP1 serves as a favorable prognostic marker and induces autophagy to suppress cell proliferation and tumor growth in KIRC.

Hepatitis D virus dual-infection among Chinese hepatitis B patient related to hepatitis B surface antigen, hepatitis B virus DNA and age.

BACKGROUND: The screening practices for hepatitis D virus (HDV) are diverse and non-standardized worldwide, and the exact prevalence of HDV is uncertain. AIM: To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D. METHODS: We collected 5594 serum samples from patients with hepatitis B in Jilin Province, China (3293 males and 2301 females, age range of 2 to 89 years). We then conducted tests for hepatitis B surface antigen (HBsAg), hepatitis B Virus (HBV) DNA, anti-hepatitis D antigen (HDAg), and HDV RNA. RESULTS: We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6% (3.2-4.2%) and 1.2% (0.9-1.5%), respectively, 87.69% of hepatitis D patients were 51-70 years old. HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL (2.0%) was higher than those above 2000 IU/mL (0.2%). Among anti-HDAg positive patients, the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level. There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients. CONCLUSION: Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection, comprehensive evaluation of patients' clinical and laboratory parameters is necessary for proper diagnosis and treatment.

The prognosis of breast cancer patients with bone metastasis could be potentially estimated based on blood routine test and biochemical examination at admission.

PURPOSE: Due to the poor and unpredictable prognosis of breast cancer (BC) patients with bone metastasis, it is necessary to find convenient and available prognostic predictors. This study aimed to recognize the clinical and prognostic factors related to clinical laboratory examination and to construct a prognostic nomogram for BC bone metastasis. METHODS: We retrospectively analyzed 32 candidate indicators from clinical features and laboratory examination data of 276 BC patients with bone metastasis. Univariate and multivariate regression analyses were performed to identify significant prognostic factors related to BC with bone metastasis. Nomogram was constructed and estimated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS: Patients were randomly grouped into training (n = 197) and validation cohorts (n = 79). In training cohort, the multivariate regression analysis revealed that age, other organ metastasis sites, serum level of lactate dehydrogenase, globulin, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and monocyte ratio were independent prognostic factors for BC with bone metastasis. The prognostic nomogram in training cohort exhibited areas under the ROC curve (AUCs) of 0.797, 0.782, and 0.794, respectively, for predicting 1-, 3-, and 5-year overall survival. In validation cohort, the nomogram still showed acceptable discrimination ability (AUCs: 0.723, 0.742, and 0.704) and calibration. CONCLUSION: This study constructed a novel prognostic nomogram for BC patients with bone metastasis. It could serve as a potential tool of survival assessment to help individual treatment decision-making for clinicians.

Our study investigated potential prognostic value of indicators from biochemical and blood routine examination for breast cancer patients with bone metastasis.Our study established a nomogram based on the indicators from biochemical and blood routine examination, which might enhance the ability to predict prognosis of breast cancer patients with bone metastasis.

Risk factors and survival analysis of haemodialysis complicated with infective endocarditis.

The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.

The effect of triethylamine on dye-sensitized upconversion luminescence and its application in nanoprobes and photostability.

Triethylamine (TEA) is an effective medium for inhibiting dye aggregation and improving the luminescence of dye-sensitized lanthanide-doped upconversion nanoparticles (UCNPs). However, excessive TEA will cause quenching of upconversion luminescence. In this paper, the possible mechanism of TEA affecting upconversion luminescence is discussed. It is found that TEA can enhance the nucleophilicity of the solvent, leading to dye shedding from the nanoparticles. Reducing the dielectric constant of the solvent can make TEA play a more positive role in upconversion luminescence and photostability of dye-sensitized UCNPs. When heptanol is selected as the solvent for CyBSO-sensitized ß-NaYF4:20%Yb3+,2%Er3+ (UNs), TEA can increase the upconversion luminescence by 6.0 times relative to that in methanol. More importantly, the optimal content of TEA in heptanol is 3700 times more than that in methanol. Under the action of large amounts of TEA in heptanol, a novel upconversion nanoprobe for detecting ascorbic acid is developed with a limit of detection of 0.103 µM and high selectivity over potential interfering species. Meanwhile, the high concentration of TEA in heptanol can improve the photostability of CyBSO-sensitized UNs by 10.4 times, which is of paramount importance for the practical application of dye-sensitized UCNPs.

Differences in Pathogenicity and Vaccine Resistance Discovered between Two Epidemic Strains of Marek's Disease Virus in China.

Despite highly effective vaccines, Marek's disease (MD) causes great economic loss to the poultry industry annually, largely due to the continuous emergence of new MD virus (MDV) strains. To explore the pathogenic characteristics of newly emerged MDV strains, we selected two strains (AH/1807 and DH/18) with clinically different pathotypes. We studied each strain's infection process and pathogenicity and observed differences in immunosuppression and vaccine resistance. Specific pathogen-free chickens, unvaccinated or vaccinated with CVI988, were challenged with AH/1807 or DH/18. Both infections induced MD damage; however, differences were observed in terms of mortality (AH/1807: 77.8%, DH/18: 50%) and tumor rates (AH/1807: 50%, DH/18: 33.3%). The immune protection indices of the vaccine also differed (AH/1807: 94.1, DH/18: 61.1). Additionally, while both strains caused interferon-ß and interferon-γ expression to decline, DH/18 infection caused stronger immunosuppression than AH/1807. This inhibition persisted even after vaccination, leading to increased replication of DH/18 that ultimately broke through vaccine immune protection. These results indicate that both strains have different characteristics, and that strains such as DH/18, which cause weaker pathogenic damage but can break through vaccine immune protection, require further attention. Our findings increase the understanding of the differences between epidemic strains and factors underlying MD vaccination failure in China.

[Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults].

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Laparoscopic liver resection for hepatocellular carcinoma complicated with significant portal hypertension: A propensity score-matched survival analysis.

BACKGROUND: Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. METHODS: HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias. RESULTS: A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group (P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate (n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification (P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05). After PSM, alpha-fetoprotein (AFP) ≥ 400 µg/L [hazard ratio (HR) = 4.71, 95% confidence interval (CI): 2.69-8.25], ascites (HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. CONCLUSIONS: LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.

Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis.

BACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target. AIM: To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH. METHODS: Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis. RESULTS: We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease. CONCLUSION: The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Enantioselective Synthesis of N-N Bisindole Atropisomers.

N-N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N-N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N-N bisindole atropisomers via the palladium-catalyzed de novo construction of one indole skeleton is presented. A wide variety of N-N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, and non-biaryl-indole atropisomers possessing a chiral N-N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol.

Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways.

In a rotenone-induced Parkinson's disease (PD) rat model, behavioral investigation, pathological examination, inflammatory factor analysis, and mitochondrial structure and function investigation verified the anti-PD efficacy of nardosinone. A combined transcriptome and proteome analysis proposed that the anti-PD target of nardosinone is the slc38a2 gene and may involve the GABAergic synaptic pathway and cAMP-signaling pathway. Analysis of targeted slc38a2 knockout cells and expression of key enzyme-encoding genes in both pathways verified the target and pathways proposed by the 'omics analysis. This further confirms that nardosinone can regulate the slc38a2 gene, a potential new target for the treatment of Parkinson's disease, and plays an anti-PD role through the GABAergic synaptic and cAMP pathways.

Cu(I)-Catalyzed Asymmetric Arylation of Pyrroles with Diaryliodonium Salts toward the Synthesis of N-N Atropisomers.

We report herein that copper(I) catalysis using a bis(phosphine) dioxide ligand can catalyze the desymmetric C-H arylation of prochiral bipyrroles. More than 50 nitrogen-nitrogen atropisomers were achieved in good to excellent yields with excellent enantioselectivities (≤97% yield, ≤98% ee). The reaction proceeds under mild conditions with good functional group compatibility on arenes and diaryliodonium salts. Moreover, this principle enables iterative arylation of the bipyrroles to enantioselectively arylate different positions during the catalysis of copper.

Gut microbiome alterations in colitis rats after moxibustion at bilateral Tianshu acupoints.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is closely related to the gut microbiota. Moxibustion has been used to improve the inflammation and gastrointestinal dysfunctions in gastrointestinal disorders such as UC. In this study, we investigated whether moxibustion could improve the gut microbial dysbiosis induced by dextran sulphate sodium. METHODS: Twenty-five male rats were randomly assigned into five groups. The UC rat model was established by administering DSS solution. The rats in the moxibustion and normal rats with moxibustion groups were treated with moxibustion at Tianshu (bilateral, ST25) points, and the mesalazine group rats were treated with mesalazine once daily for 7 consecutive days. Disease activity index (DAI) and haematoxylin and eosin staining were used to evaluate the effect of moxibustion. Gut microbiota profiling was conducted by metagenomic high throughput sequencing technology. The gut microbiota composition, diversity and function were analyzed and compared using metagenomics methodologies. RESULTS: The DAI scores and histopathology scores in the moxibustion and mesalazine groups were significantly decreased compared with the UC group (P < 0.01). Moxibustion treatment increased abundance levels of Bacteroidetes, Actinobacteria, Ascomycota, Synergistetes and decreased abundance of Firmicutes, Proteobacteria. At the genus level, the abundance of Bacteroides, Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2, were increased and Bacteroides_bacterium_H3, Parabacteroides, Porphyromonas, Alistipes, Parasutterella were decreased in the UC group in comparsion with those in the NG group. Moxibustion increased the abundance of Bacteroides and Bacteroides_bacterium_H3 and decreased Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2. In UC group, the specie Bacteroides_massiliensis was negatively (P < 0.05) correlated with IL-23, Bacteroides_eggerthii_CAG109 and Bacteroides_eggerthii were negatively (P < 0.05) correlated with TGF-ß. And the species Prevotella_sp_CAG1031 and Bacteroides_bacterium_H2 were significant positively (P < 0.05) correlated with IL-23. In addition, compare with the normal group, genes involved in certain metabolic pathways, such as energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, were under-represented in the UC group, and these changes in the metabolic pathways could be reversed by moxibustion treatment and mesalazine treatment. CONCLUSIONS: Our findings suggest that moxibustion treatment may protect the host from mucosal inflammation by modulating the intestinal microbiota community.

The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have been shown to promote NAFLD pathogenesis and progression through increasing lipid accumulation, oxidative stress, mitochondrial damage, and inflammation. The miR-23-27-24 clusters, composed of miR-23a-27a-24-2 and miR-23b-27b-24-1, have been implicated in various biological processes as well as many diseases. Herein, we review the current knowledge on miR-27, miR-24, and miR-23 in NAFLD pathogenesis and discuss their potential significance in NAFLD diagnosis and therapy.

Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B.

BACKGROUND: Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application. AIM: The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion. METHODS: This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530). Serum qHBcrAg, pgRNA, HBV DNA, hepatitis B core antigen, HBeAg, liver cccDNA, and HBV DNA were measured. The correlations of serum qHBcrAg with other biomarkers were analyzed. RESULTS: A total of 139 patients were included. The mean qHBcrAg levels were 5.32 ± 1.18 log10 U/mL at baseline and decreased during treatment (all P < 0.0001). Serum qHBcrAg levels were positively correlated with pgRNA (r = 0.597, P < 0.0001) and cccDNA (r = 0.527, P < 0.0001) levels. The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant (r = 0.399, P < 0.0001). HBcrAg predicted HBeAg seroconversion, with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion [odds ratio (OR) = 2.402, 95% confidence interval (CI): 1.314-4.391, P = 0.004; OR = 3.587, 95%CI: 1.315-9.784, P = 0.013]. CONCLUSION: Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

ß2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis.

Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment and so far no effective drug is available for treatment of the serious side effect. Previous studies have demonstrated ß2-adrenoreceptor (ADRB2) agonists can attenuate neuropathic pain. However, the role of ADRB2 in paclitaxel -induced neuropathic pain (PINP) remains unclear. In this study, we investigated the effect of formoterol, a long-acting ADRB2 agonist, and related mechanisms in PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to evaluate mechanical allodynia. Western blot was used to examine the expression of ADRB2, peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factors 1 (NRF1) and mitochondrial transcription factor A (TFAM) and the immunofluorescence was to detect the cellular localization of ADRB2 and PGC-1α in the spinal cord. Moreover, we measured mitochondrial DNA (mtDNA) copy number by qPCR. In our study, formoterol attenuated established PINP and delayed the onset of PINP. Formoterol restored ADRB2 expression as well as mtDNA copy number and PGC-1α, NRF1, and TFAM protein expression, which are major genes involved in mitochondrial biogenesis, in the spinal cord of PINP rats. Moreover, we found the analgesic effect of formoterol against PINP was partially abolished by PGC-1α inhibitor SR-18292. Collectively, these results demonstrated the activation of ADRB2 with formoterol ameliorates PINP at least partially through induction of mitochondrial biogenesis.