A universal plasma metabolites-derived signature predicts cardiovascular disease risk in MAFLD.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, which is more practical for identifying patients with fatty liver disease with high risk of disease progression. Fatty liver is a driver for extrahepatic complications, particularly cardiovascular diseases (CVD). Although the risk of CVD in MAFLD could be predicted by carotid ultrasound test, a very early stage prediction method before the formation of pathological damage is still lacking. METHODS: Stool microbiomes and plasma metabolites were compared across 196 well-characterized participants encompassing normal controls, simple MAFLD patients, MAFLD patients with carotid artery pathological changes, and MAFLD patients with diagnosed coronary artery disease (CAD). 16S rDNA sequencing data and untargeted metabolomic profiles were interrogatively analyzed using differential abundance analysis and random forest (RF) machine learning algorithm to identify discriminatory gut microbiomes and metabolomic. RESULTS: Characteristic microbial changes in MAFLD patients with CVD risk were represented by the increase of Clostridia and Firmicutes-to-Bacteroidetes ratios. Faecalibacterium was negatively correlated with mean-intima-media thickness (IMT), TC, and TG. Megamonas, Bacteroides, Parabacteroides, and Escherichia were positively correlated with the exacerbation of pathological indexes. MAFLD patients with CVD risk were characterized by the decrease of lithocholic acid taurine conjugate, and the increase of ethylvanillin propylene glycol acetal, both of which had close relationship with Ruminococcus and Gemmiger. Biotin l-sulfoxide had positive correlation with mean-IMT, TG, and weight. The general auxin pesticide beta-naphthoxyacetic acid and the food additive glucosyl steviol were both positively correlated with the increase of mean-IMT. The model combining the metabolite signatures with 9 clinical parameters accurately distinguished MAFLD with CVD risk in the proband and validation cohort. It was found that citral was the most important discriminative metabolite marker, which was validated by both in vitro and in vivo experiments. CONCLUSIONS: Simple MAFLD patients and MAFLD patients with CVD risk had divergent gut microbes and plasma metabolites. The predictive model based on metabolites and 9 clinical parameters could effectively discriminate MAFLD patients with CVD risk at a very early stage.

Analysis of gastrin-17 and its related influencing factors in physical examination results.

BACKGROUND: To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17 and pepsinogen, and to study the influences of Helicobacter pylori (H. pylori) infection and various inflammatory factors on G17 secretion level. METHODS: A total of 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All subjects were tested for G17, pepsinogen I (PGI), pepsinogen II (PGII), PGI/PGII ratio (PGR), H. pylori, serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The difference of G17 secretion in different subjects and its correlation with PG were analyzed to investigate H. pylori infection and expound the effects of inflammatory indicators on G17. RESULTS: There was no significant difference in G17 secretion level in people with different sex, age and BMI (p > .05). G17 positively correlated with PGI and PGII, but negatively correlated with PGR. The G17 level of H. pylori-positive subjects was 10.16 ± 12.84, and prominently higher than that of H. pylori-negative subjects (3.27 ± 6.65). SAA and H. pylori infection were the greater risk factors for G17 abnormality among various indicators. CRP and ESR had no effect on G17 abnormality. CONCLUSIONS: G17 secretion is closely related to PG and H. pylori. Combined screening contributes to early screening of gastrointestinal diseases in normal people or groups at high risk for gastric cancer, but the influence of inflammatory indicators on G17 should be excluded to improve the reliability of the results.

Oral nicotinamide mononucleotide (NMN) to treat chronic insomnia: protocol for the multicenter, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: The treatment of insomnia, which is the most common sleep disorder, includes drug and behavioral treatment, but each treatment measure has its limitations. So new treatment method needs to be taken to improve the treatment effect. MN supplementation is a potential promising new method for the treatment of insomnia, resulting in a rising need for methodological research towards verifying its efficacy. METHODS/DESIGN: We describe a proposal for a multicenter, patient-assessor-blinded, randomized controlled trial with two parallel arms. A total of 400 chronic insomnia patients will be allocated 1:1 to the intervention group (treatment with oral NMN 320 mg/day) or control group (treatment with oral placebo). All subjects are clinical chronic insomnia patients who meet all inclusion criteria. All subjects are treated by taking NMN or placebo. The primary outcome is the score on the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes are the score on the Insomnia Severity Index (ISI) and Epworth Sleeping Scale (ESS), the total sleep time (TST), sleep efficiency (SE), sleep latency, and REM sleep latency to assess sleep quality changes. Subjects are assessed at two time points: baseline and follow-up. The duration of the clinical trial is 60 days. DISCUSSION: This study will provide more evidence on the effects of NMN on improving sleep quality among patients with chronic insomnia. If proven effective, NMN supplement can be used as a new treatment for chronic insomnia in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2200058001. Registered on 26 March 2022.

Genetic diversity and population structure of Tongcheng pigs in China using whole-genome SNP chip.

Tongcheng (TC) pigs, distinguished by their superior meat quality, are a Chinese indigenous pig breed. Recently, the genetic resources of TC pigs are under tremendous threat due to the introduction of cosmopolitan pig breeds and African swine fever disease. To promote their management and conservation, the present study assessed genetic diversity and population structure of TC pigs using single nucleotide polymorphism (SNP) markers. A total of 26, 999 SNPs were screened from 51, 315 SNPs in 68 TC pigs. The multi-dimensional scaling (MDS) analysis and neighbor-joining tree revealed that all 68 pigs were from a purebred population. The effective population size decreased over time, and it was 96 prior to generation 20. Both linkage disequilibrium (LD) and neutrality test indicated a low selection of TC pigs with average LD value of 0.15 ± 0.23. Genetic diversity results exhibited a minor allele frequency (MAF) of 0.23, observed heterozygosity (HO) of 0.32, expected heterozygosity (He) of 0.31, and nucleotide diversity (Pi) of 0.31. All these parameters indicated a remarkably high genetic diversity of TC pigs. Additionally, 184 runs of homozygosity (ROH) segments were detected from the whole genome of TC pigs with an average ROH length of 23.71Mb, ranging from 11.26Mb to 69.02 Mb. The highest ROH coverage was found on chromosome 1 (10.12%), while the lowest was on chromosome 18 (1.49%). The average inbreeding coefficients based on ROH (FROH) was 0.04%. Fourteen ROH islands containing 240 genes were detected on 9 different autosomes. Some of these 240 genes were overlapped with the genes related to biological processes such as immune function, reproduction, muscular development, and fat deposition, including FFAR2, FFAR4, MAPK8, NPY5R, KISS1, and these genes might be associated with such traits as meat quality and disease resistance in TC pigs. Taken together, population structure and genetic diversity results suggested that the TC pig represented a valuable genetic resource. However, TC pig breed conservation program remains to be further optimized to ensure adequate genetic diversity and avoid inbreeding depression. Our findings provide theoretical basis for formulating management and conservation strategies for TC pigs.

Eradication of Helicobacter pylori alleviates lipid metabolism deterioration: a large-cohort propensity score-matched analysis.

BACKGROUND: The impact of Helicobacter pylori (H. pylori) eradication on metabolism of lipid and the potential predictor of such changes remain unclear. METHODS: This study retrospectively included subjects who underwent at least two 13C urea breath tests between 2015 and 2019 at Wuhan Union Hospital. Based on two H. pylori 13C examination results, subjects were divided into propensity score-matched persistently negative (HPN), persistently positive (HPP), and eradication (HPE) groups. The changes in lipid measurements from before to after H. pylori eradication, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides, were compared within and between groups. Forty-two candidate factors were tested for their ability to predict lipid metabolism changes after H. pylori eradication. RESULTS: After propensity score matching, 3412 matched cases were analyzed. Within-group comparisons showed significantly decreased HDL (P <  0.001) and increased LDL (P <  0.001) at the second examination in both the HPE and HPP groups. Between-group comparisons showed that the HDL decrease of the HPE group was significantly larger and smaller when compared with the HPN (P = 0.001) and HPP (P = 0.004) group, respectively. Uni- and multivariate analyses showed that low diastolic blood pressure (DBP) (P = 0.002) and high mean platelet volume (MPV) (P = 0.001) before eradication were associated with increased HDL after eradication. Low total protein (TP) (P <  0.001) was associated with decreased LDL after eradication. CONCLUSIONS: Compared with sustained H. pylori infectious states, H. pylori eradication alleviated the lipid metabolism deterioration but did not restore it to the uninfected level within 1.5 years after eradication. Patients with low DBP, high MPV, and low TP may reap a greater lipid-metabolism benefit from H. pylori eradication.

Helicobacter pylori infection is not an independent risk factor of non-alcoholic fatty liver disease in China.

BACKGROUND: The role of Helicobacter pylori (H. pylori) infection in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. The exact relationship requires further investigation. This study aimed to determine the association between them in China. METHODS: A retrospective study was conducted on 71,633 participants who underwent physical examinations. 13C urea breath test (13C-UBT) was conducted to detect H. pylori infection, and ultrasonography was used to detect NAFLD. RESULTS: Body mass index (BMI), blood pressure (BP), and triglyceride (TG) levels were higher in participants with H. pylori infection than in those without H. pylori infection. While the levels of high-density lipoprotein cholesterol (HDL-C) for participants with H. pylori infection was lower than without H. pylori infection (P < 0.001). After adjusting for confounding factors (age, sex, BMI, BP, Scr, BUN, LDL-C, HDL-C, triglycerides, FBG and HbA1c), multivariate logistic regression analysis indicated that there was no independent relationship between them (P = 0.574). Subgroup analysis (stratified by sex, age, BMI, hypertension, diabetes and dyslipidemia) showed that H. pylori infection was not included as an independent risk factor for NAFLD. Moreover, the different grades of NAFLD were not related to H. pylori infection. CONCLUSIONS: These results indicate that H. pylori infection is not an independent risk factor for NAFLD in China.

Association of urinary rubidium concentrations with hypertension risk and blood pressure levels: A cross-sectional study in China.

BACHGROUND: Rubidium resembles potassium. We hypothesized that rubidium might play a role in blood pressure control. METHODS: We measured urinary rubidium concentrations and blood pressure levels using validated techniques and methods in 2002 eligible participants. Multivariable logistic and linear regression models were applied to explore the associations. The restricted cubic spline model was utilized to investigate the dose-response relationship. Furthermore, we explored the associations of rubidium with risk factors (glomerular filtration rate, uric acid, and homocysteine) for hypertension and relevant biochemical indexes. RESULTS: After adjustment for potential confounders and urinary potassium and sodium levels, doubling of urinary rubidium concentrations was significantly associated with decreased hypertension risk [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.61, 0.93] and reduced systolic blood pressure (SBP) levels of 2.92 (95% CI: 1.56, 4.26) mm Hg. Each 1.00 mg/L increase in rubidium concentrations was associated with a 1.25 mm Hg decreased SBP levels, which was at least 200 times more effective than potassium. Furthermore, urinary rubidium concentrations were negatively associated with the risk factors for hypertension. CONCLUSIONS: Rubidium might have more prominent effects on lowering blood pressure levels than potassium. Prospective studies and experimental research focusing on our findings are needed.

Saccharomyces boulardii Combined With Quadruple Therapy for Helicobacter pylori Eradication Decreased the Duration and Severity of Diarrhea: A Multi-Center Prospective Randomized Controlled Trial.

Background: Whether probiotics helped the Helicobacter pylori (H. pylori) eradication was still highly controversial. The non-bacterial Saccharomyces boulardii (S. boulardii) has demonstrated its efficacy in the treatment of antibiotic-associated and infectious diarrhea. We aimed to evaluate the effects of S. boulardii combined with quadruple therapy for H. pylori eradication and associated side effects. Methods: Three hundred and sixty H. pylori-infected patients were recruited in this multicenter, randomized controlled trial. The patients who underwent H. pylori eradication treatment were randomized in a ratio of 1:1 into two separate groups that received standard quadruple therapy (Group A) and quadruple therapy plus S. boulardii sachets (Group B) for 14 days. The everyday medication and side-effect records were collected for compliance and adverse effect analysis. All patients accepted 13C/14C-urea breath tests 4 weeks after the therapy completion. Results: Saccharomyces boulardii and quadruple therapy-combined intervention significantly reduced the incidences of overall side effects (27.8 vs. 38.5%, p = 0.034) and diarrhea (11.2 vs. 21.2%, p = 0.012) in Group B compared with quadruple therapy alone in Group A, especially reduced the diarrhea duration (5.0 days vs. 7.7 days, p = 0.032) and incidence of severe diarrhea (4.7 vs. 10.1%, p = 0.040). Intention-to-treat (ITT) analysis and per-protocol (PP) analysis both indicated no statistical differences of eradication rate between Groups A and B (ITT: 82.7 vs. 85.8%, p = 0.426; PP: 89.7 vs. 94.2%, p = 0.146). The joint use of S. boulardii and quadruple therapy markedly improved the overall pre-eradication alimentary symptoms (hazard ratio (HR): 2.507, 95% CI: 1.449-4.338) recovery. Conclusion: Saccharomyces boulardii ameliorated H. pylori eradication-induced antibiotic-associated side effects especially reduced the incidence of severe diarrhea and the duration of diarrhea. However, there was no significant effect of S. boulardii on the rate of H. pylori eradication. Trial Registration: The protocol had retrospectively registered at ClinicalTrails.gov, Unique identifier: NCT03688828, date of registration: September 27, 2018; https://clinicaltrials.gov/show/NCT03688828.

Morphine Suppresses Liver Cancer Cell Tumor Properties In Vitro and In Vivo.

Morphine is an analgesic widely adopted to relieve cancer pain. A number of discrepancies, however, are presented by the published literature, with reports suggesting that opioids may either promote or inhibit the spread of cancer. It is of great significance to determine whether morphine may increase the risk of metastasis while utilized in liver cancer surgical treatment. In this study, we explore the effects of morphine on liver cancer cells in vitro and in vivo. Our results showed that morphine does not promote proliferative ability to cultured liver cancer cells. While morphine could increase the apoptosis rate of Hep3B/HepG2 cells. Furthermore, morphine could significantly inhibit the migratory and invasion ability of Hep3B/HepG2 cells. Subsequent investigations disclosed that morphine could inhibit sphere formation ability of Hep3B/HepG2 cells by using sphere formation assay. Based on nude mouse models, we demonstrated that morphine significantly reduced pulmonary tumorigenicity of Hep3B/HepG2 cells. In conclusion, our results found that morphine at clinical concentrations could suppress liver cancer cell tumor properties in vitro and in vivo, indicating the safety of morphine utilization in HCC patients' pain management.

Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women.

BACKGROUND: The incidence rate of cervical cancer is increasing yearly. The persistent infection of high-risk human papillomavirus (HPV) is the main factor leading to cervical cancer. HPV infection is double peak type. This study aimed at analyzing the HPV distribution characteristics, infection rate, and risk of age in pre- and postmenopausal women. So as to provide reference for the prevention of HPV infection and cervical cancer screening strategy. METHODS: A retrospective analysis of 4614 women who underwent cervical cytology, and HPV examination from January 2018 to October 2019 at the healthcare department of Wuhan Union Hospital was done. We explored the characteristics and distribution of HPV infections around the menopause, then comparing the infection rate of HPV in postmenopause and over 65 years old, in order to analyze the influence of different ages on HPV infection. RESULTS: Generally, the HPV infection rate was 13.10% (539/4115), whereby the high-risk subtype constituted 73.84% (398/539) of all positive cases. On the other hand, the HPV39 infection was more common in postmenopausal women; however, there was no significant difference in the distribution of the other types in the pre- and postmenopausal women. The first four types were 52/53/58/16. The results further showed that the rates of HPV infection before and after menopause were 12.34% (367/2975) and 15.09% (172/1140), respectively, which had no significant difference (P = 0.056), but more susceptible to high-risk HPV infection after the age of 65 (P = 0.041). Except for 40 years old to menopause, the infection rate of high-risk HPV in this age group was different from that in postmenopause (P = 0.023, 0.729 (0.555, 0.957)), other age groups had no significant effect on high-risk HPV infection. CONCLUSIONS: It was concluded that whether menopause has nothing to do with HPV infection. Moreover, the risk of high-risk HPV infection in women aged 40 to premenopausal is relatively low, but the infection rate increases after 65. Hence the cutoff screening age should be appropriately prolonged.

Symptom improvement after helicobacter pylori eradication in patients with functional dyspepsia-A multicenter, randomized, prospective cohort study.

OBJECTIVE: To observe the improvement of functional dyspepsia (FD) after helicobacter pylori (HP) eradication in FD patients. METHODS: 644 FD patients were recruited of whom 585 completed follow up. They were divided into postprandial distress syndrome (PDS) group and epigastric pain syndrome (EPS) group. Patients with HP infection were randomly allocated into eradication group and non-eradication group. Patients in the eradication group were randomly assigned into two groups and treated with triple therapy and sequential therapy, respectively. Patients in non-eradication group and HP non-infection group were treated with Domperidone (PDS patients) or Talcid (EPS patients). Clinical symptoms were evaluated. RESULTS: When compared with patients with unsuccessful HP eradication and without eradication, significant improvement in symptoms was found at 8 w, 12 w, and 26 w in patients with successful HP eradication in EPS group (P < 0.05). However, in PDS group, improvement in symptoms was comparable among patients expect at 26 w after successful HP eradication (P < 0.05). Therapeutic efficacy in patients without HP eradication was poorer than that in HP negative patients in EPS group (P < 0.05), while in PDS group, symptoms were relived at 26 w and 52 w (P < 0.05). CONCLUSIONS: HP is one of pathogenic factors of FD and HP eradication may benefit FD patients, regardless therapeutic regimes, especially in EPS patients.

Electroacupuncture accelerates solid gastric emptying and improves dyspeptic symptoms in patients with functional dyspepsia.

The aims of this study were to investigate the effects of electroacupuncture (EA) at ST36 and PC6 points on solid gastric emptying and dyspeptic symptoms in patients with functional dyspepsia. Nineteen patients with functional dyspepsia (FD) were involved in the study, consisting of two parts: (1) acute effects of EA on solid gastric emptying in FD patients with delayed gastric emptying and (2) short-term (2-week) effects of EA on symptoms in FD patients with normal gastric emptying. Results were as follows. (1) Ten of the19 patients showed delayed gastric emptying of solids, and acute EA significantly improved delayed gastric emptying; the halftime for gastric emptying was reduced from 150.3+/-48.4 to 118.9+/-29.6 min (P=0.007). (2) In the nine patients with normal gastric emptying, 2-week EA significantly decreased the symptom score, from 8.2+/-3.3 at baseline to 1.6+/-1.1 (P < 0.001) at the end of treatment. We conclude that EA at the ST36 and PC6 points accelerates solid gastric emptying in FD patients with delayed gastric emptying and relieves dyspeptic symptoms in FD patients with normal gastric emptying.