Patients with auto-brewery syndrome (ABS) become inebriated after the ingestion of an alcohol-free, high-carbohydrate diet. Our previous work has shown that high-alcohol-producing (HiAlc) Klebsiella pneumoniae can generate excessive endogenous ethanol and cause non-alcoholic fatty liver disease (NAFLD). Therefore, it is reasonable to speculate that such bacteria might play an important role in the pathogenesis of ABS. The characteristics and metabolites of the intestinal flora from a clinical cohort of patients with ABS were analysed during different stages of disease and compared to a group of healthy controls. An in vitro culture system of relevant samples was used for screening drug sensitivity and ABS-inducing factors. Rabbit intestinal and murine models were established to verify if the isolated strains could induce ABS in vivo. We observed intestinal dysbiosis with decreased abundance of Firmicutes and increased of Proteobacteria in patients with ABS compared with healthy controls. The abundance of the genus Klebsiella in Enterobacteriaceae was strongly associated with fluctuations of patient's blood alcohol concentration. We isolated three species of HiAlc Klebsiella from ABS patients, which were able to induce ABS in mice. Monosaccharide content was identified as a potential food-related inducing factor for alcohol production. Treatments with antibiotics, a complex probiotic preparation and a low-carbohydrate diet not only alleviated ABS, but also erased ABS relapse during the follow-up observation of one of the patients. Excessive endogenous alcohol produced by HiAlc Klebsiella species was an underlying cause of bacterial ABS. Combined prescription of appropriate antibiotics, complex probiotic preparation and a controlled diet could be sufficient for treatment of bacteria-caused ABS. The funders are listed in the acknowledgement.

Background: The relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) has not been clearly elucidated in middle-aged and older adults. This study aimed to evaluate the non-linear dose-response relationship between BMI and LDL-C in males and females. Methods: Data was obtained from two nationally representative surveys in China—the China Health and Nutrition Survey (CHNS, 2009) and China Health and Retirement Longitudinal Study (CHARLS, 2011–2012). To evaluate the sex differences in the association between BMI and LDL-C, the generalized additive models with a smooth function for continuous BMI and smooth-factor interaction for sexes with BMI were used. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints among females and males. Results: A total of 12,273 participants (47.1% male) aged 45 to 75 years were included. The generalized additive models revealed that a non-linear relationship between BMI and LDL-C level in both sexes after adjustment for age, residence, education levels, marital status, drinking, smoking status, and cohort (CHNS or CHARLS). Slopes of the association between BMI and LDL-C association changed at BMI 20.3 kg/m² (95% CI: 18.8 to 21.8) in females and 27.1 kg/m² (95% CI: 25. 8 to 28.4) in males. Below these BMI breakpoints, LDL-C levels increased 1.84 (95% CI: 1.45 to 2.31) in males and 3.49 (95% CI: 1.54 to 5.45) mg/dL per kg/m² in females. However, LDL-C levels declined − 1.50 (95% CI: − 2.92 to − 0.09) mg/dL per kg/m² above BMI of 27.1 kg/m² in males. The non-linear association BMI and LDL-C in males and females was varied by cohort source, age groups, and the number of metabolic syndrome criteria. Conclusions: In the Chinese middle aged and older adults, the BMI and LDL-C relationship was inverted U-shaped with a high level of LDL-C at a BMI of 27.1 kg/m² in males, and an approximately linear association was observed in females.

This study aimed to explore the disrupted prefrontal cortex activity specific to patients with Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD) compared with those without and to further examine the associations between these alterations and neuropsychological measurements. Ninety-six patients with early PD underwent both structural and functional MRI, and also neuropsychological assessments in the Parkinson's Progression Markers Initiative (PPMI) database. Of these, 46 patients who completed 1- and 3-year fMRI follow-up examinations were categorized as PD with probable RBD (PD-pRBD⁺) and without (PD-pRBD⁻). The left dorsolateral prefrontal cortex (DLPFC) seed-to-voxel functional connectivity analysis was conducted to evaluate the progressive neural alterations specific to PD-pRBD⁺ compared with PD-pRBD⁻ over time. Furthermore, relationships between these alterations and neuropsychological performance were examined. Compared with patients with PD-pRBD⁻, patients with PD-pRBD⁺ initially exhibited connectivity deficits between the left DLPFC and the medial frontopolar cortex. Moreover, these patients further exhibited disrupted DLPFC connectivity in the lateral frontopolar cortex at the 3-year follow-up evaluation. Correlation analysis revealed that connectivity between the left DLPFC and frontopolar cortex was positively related to executive function in PD-pRBD⁺ after adjusting for nuisance variables. Progressive prefrontal cortex dysfunction associated with RBD in early PD may provide an effective subtype-specific biomarker of neurodegenerative progression, which may shed light on the neuropathological mechanisms underlying the clinical heterogeneity of this disease.

This study aimed to further investigate the effect of PLD1 on the biological characteristics of human cervical cancer (CC) cell line, CASKI and the potential related molecular mechanism. CRISPR/Cas9 genome editing technology was used to knock out the PLD1 gene in CASKI cells. Cell function assays were performed to evaluate the effect of PLD1 on the biological function of CASKI cells in vivo and in vitro. A PLD1‐overexpression rescue experiment in these knockout cells was performed to further confirm its function. Two PLD1‐knockout CASKI cell lines (named PC‐11 and PC‐40, which carried the ins1/del4 mutation and del1/del2/ins1 mutation, respectively), were constructed by CRISPR/Cas9. PLD1 was overexpressed in these knockout cells (named PC11‐PLD1 and PC40‐PLD1 cells), which rescued the expression of PLD1 by approximately 71.33% and 74.54%, respectively. In vivo, the cell function assay results revealed that compared with wild‐type (WT)‐CASKI cells, the ability of PC‐11 and PC‐40 cells to proliferate, invade and migrate was significantly inhibited. The expression of H‐Ras and phosphorylation of Erk1/2 (p‐Erk1/2) was decreased in PC‐11 and PC‐40 cells compared with WT‐CASKI cells. PC‐11 and PC‐40 cells could sensitize CASKI cells to cisplatin. More importantly, the proliferation, migration and invasion of PC11‐PLD1 and PC40‐PLD1 cells with PLD1 overexpression were significantly improved compared with those of the two types of PLD1 knockout cells. The sensitivity to cisplatin was decreased in PC11‐PLD1 and PC40‐PLD1 cells compared with PC‐11 and PC‐40 cells. In vivo, in the PC‐11 and PC‐40 tumour groups, tumour growth was significantly inhibited and tumour weight (0.95 ± 0.27 g and 0.66 ± 0.43 g vs. 1.59 ± 0.67 g, p = 0.0313 and 0.0108) and volume (1069.41 ± 393.84 and 1077.72 mm³ ± 815.07 vs. 2142.94 ± 577.37 mm³, p = 0.0153 and 0.0128) were significantly reduced compared to those in the WT‐CASKI group. Tumour differentiation of the PC‐11 and PC40 cells was significantly better than that of the WT‐CASKI cells. The immunohistochemistry results confirmed that the expression of H‐Ras and p‐Erk1/2 was decreased in PC‐11 and PC‐40 tumour tissues compared with WT‐CASKI tumour tissues. PLD1 promotes CC progression by activating the RAS pathway. Inhibition of PLD1 may serve as an attractive therapeutic modality for CC.

The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson’s disease (PD). Eighty-two early PD patients and twenty-one healthy controls underwent structural and resting-state functional MRI scans, as well as neuropsychological assessments from the Parkinson’s Progression Markers Initiative database. A whole brain voxel-wise regression analysis was conducted to evaluate the relationship between the FC of the entorhinal cortex (EC-FC) and olfactory performance. Then, a one-way ANCOVA, based on the regions of interest, was performed with SPSS to investigate the group differences and correlation analysis that were used to analyze the relationships between the FC and neuropsychological assessments. In addition, regression models were used to evaluate the risk factors for the decreased olfactory function. A significantly negative correlation was observed between the olfactory performance and the left EC-FC in the right dorsal cingulate gyrus (dCC) in patients. The PD patients with anosmia exhibited significantly higher FC values than the PD patients with normal olfaction or the PD patients with mild to moderate microsomia. Except for the olfactory performance, no significant correlation was detected between the neuropsychological assessments and the FC values. A linear regression analysis revealed that the increased FC and Geriatric Depression Scale are independently associated with lower the University of Pennsylvania Smell Identification Test scores. The current findings enhanced the understanding of olfactory dysfunction-related pathophysiological mechanisms in early PD and suggested that the left EC-FC in the right dCC may be a potential neuroimaging biomarker for olfactory performance.

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis.Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram.Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model.Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.