Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To investigate the prevalence of autonomic dysfunction and its influencing factors in the elderly in Jizhou community of Tianjin. Methods: By using a cross-sectional study, a questionnaire survey was conducted in the elderly in order to investigate the prevalence of autonomic dysfunction and its influencing factors. Results: A total of 1 292 elderly patients were enrolled.Of them, 196 cases had autonomic dysfunction(15.2%, 196/1 292). The main symptoms of autonomic dysfunction were frequent urination, urination urgency, urination incontinence(19.7%, 255/1 292)and constipation(15.9%, 205/1 292). Multivariate Logistic regression analysis showed that women(OR=1.808, 95%CI: 1.253~2.607), 75-85 years of age(OR=1.573, 95%CI: 1.109~2.232), general anesthesia history(OR=1.552, 95%CI: 1.044~2.307), sleep disorders(OR=2.906, 95%CI: 1.506~2.916), diabetes(OR=1.791, 95%CI: 1.197~2.678)and headache(OR=2.589, 95%CI: 1.482~4.520)were risk factors for autonomic dysfunction. Conclusions The prevalence of autonomic dysfunction is high in the elderly in Jizhou community of Tianjin city.It is necessary to pay great attention to potential risk factors of autonomic dysfunction in the elderly.And the autonomic dysfunction symptoms should be diagnosed and treated as early as possible.

OBJECTIVE： To establish a method for the content determination of sinapine thiocyanate， quercetin and kaempferol in rat plasma， and to study pharmacokinetics of Qili qiangxin capsule in rats in vivo. METHODS： HPLC-MS/MS method was adopted. The determination was performed on ZOBRAX XDB-C18 column with mobile phase consisted of 0.1％ formic acid solution and acetonitrile containing 0.1％ formic acid （gradient elution） at the flow rate of 0.45 mL/min. The sample size was 10 μL. Quantitative ions were sinapine thiocyanate with m/z 310.2→251.2， quercetin with m/z 301.1→150.7， kaempferol with m/z 286.2→242.0， internal standard chloramphenicol with m/z 320.9→ 151.9. 0.083， 0.167， 0.333， 0.667， 1， 1.5， 2， 3， 4， 6， 8， 12， 24 h after intragastric administration of Qili qiangxin capsule 1.3 g/kg， blood samples were collected via intraocular canthal venous plexus of 6 rats. The blood concentrations of sinapine thiocyanate， quercetin and kaempferol were determined. The pharmacokinetic parameters were calculated and fitted by using DAS 3.0 software. RESULTS： The linear range of sinapine thiocyanate， quercetin and kaempferol 0.05-100， 0.1-200， 0.1-200 ng/mL（r＝0.999 4， 0.999 7， 0.999 9）； RSDs of precision test and matrix effect were all less than or equal to 11.55％ （n＝6）， RE of stability test is less than or equal to 14.69％ （n＝3）. The pharmacokinetic parameter of sinapine thiocyanate， quercetin and kaempferol included that cmax were（1.35±0.62），（3.23±1.26），（5.27±1.66）      ng/mL； tmax were （1.50±0.00）， （0.67±0.00）， （0.67±0.00） h； t1/2 were （3.98±0.99），（3.33±0.41），（4.54±0.85） h； CL were （3 683.82±987.96）， （2 852.33±695.88），（1 611.85±129.59） mL/（h·kg）； AUC0-24 h were （3.98±1.21）， （10.96±3.42）， （13.59±5.35） h·ng/mL. CONCLUSIONS： Established method is highly sensitive， specific and reproducible， and suitable for the pharmacokinetic study of sinapine thiocyanate， quercetin and kaempferol in rat.

OBJECTIVETo evaluate the efficacy and safety of Solitaire(TM) AB neurovascular stenting-assisted coil embolization for patients with wide-necked or dissecting aneurysms.

METHODSThe clinical results and prognosis from a consecutive series of 38 patients with 40 wide-necked or dissecting aneurysms aneurysms who treated by Solitaire(TM) AB neurovascular stenting-assisted coil embolization from August 2010 to January 2012 was retrospectively analyzed. There were 12 male and 26 female patients, the age was 21 - 78 years (mean 55 years). Thirty-one cases were confirmed wide-neck aneurysms and 9 cases were dissection aneurysms by DSA. Acute subarachnoed hemorrhage due to the rupture of aneurysms was seen in 28 cases (according Hunt-Hess scale, 1 case of Class I, 20 cases of Class II, 4 cases of Class III, 3 cases of Class IV), 1 case was traumatic intracranial aneurysm, 1 case was misdiagnosed during the operation of pituitary adenoma by the approach of transsphenoid, and unruptured aneurysms were seen in 8 cases. The aneurysms were located at the posterior communicating segment of internal carotid artery (21 cases), the supraclinoid segment of internal carotid artery (6 cases), the cavernous segment of internal carotid artery (3 cases), the anterior communicating artery (1 case), and the vertebral artery (9 cases). The patients were performed DSA and Glasgow outcome score (GOS) to evaluate the prognosis 6 months after surgery.

RESULTSForty stents were used and all remodeling device were achieved successful position. Owing to acute thrombosis in 3 patients, the stents were retrieved successfully. The proportion of patients in whom Raymond class 1 occlusion was obtained in 31 cases (77.5%), Raymond class 2 occlusion in 5 cases (12.5%) and Raymond class 3 occlusion in 4 cases (10.0%). The follow-up was 3 to 12 months (median 6 months). The results of DSA indicated none of the patients' anuerysm was recurred; and GOS was applied to evaluate the prognosis of patients after 3 months. Of 38 patients, 34 recovered well, 3 moderately disabled, 1 patient died.

CONCLUSIONSIt is safe to embolize aneurysms with Solitaire(TM) AB neurovascular stenting-assisted coil; meanwhile, the stents can be retrieved when acute thrombosis to reduce the complications.

Adult ; Aged ; Aneurysm, Dissecting ; therapy ; Cerebral Angiography ; Embolization, Therapeutic ; instrumentation ; Female ; Humans ; Intracranial Aneurysm ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Young Adult

BACKGROUNDVarious methods can be applied to build predictive models for the clinical data with binary outcome variable. This research aims to explore the process of constructing common predictive models, Logistic regression (LR), decision tree (DT) and multilayer perceptron (MLP), as well as focus on specific details when applying the methods mentioned above: what preconditions should be satisfied, how to set parameters of the model, how to screen variables and build accuracy models quickly and efficiently, and how to assess the generalization ability (that is, prediction performance) reliably by Monte Carlo method in the case of small sample size.

METHODSAll the 274 patients (include 137 type 2 diabetes mellitus with diabetic peripheral neuropathy and 137 type 2 diabetes mellitus without diabetic peripheral neuropathy) from the Metabolic Disease Hospital in Tianjin participated in the study. There were 30 variables such as sex, age, glycosylated hemoglobin, etc. On account of small sample size, the classification and regression tree (CART) with the chi-squared automatic interaction detector tree (CHAID) were combined by means of the 100 times 5-7 fold stratified cross-validation to build DT. The MLP was constructed by Schwarz Bayes Criterion to choose the number of hidden layers and hidden layer units, alone with levenberg-marquardt (L-M) optimization algorithm, weight decay and preliminary training method. Subsequently, LR was applied by the best subset method with the Akaike Information Criterion (AIC) to make the best used of information and avoid overfitting. Eventually, a 10 to 100 times 3-10 fold stratified cross-validation method was used to compare the generalization ability of DT, MLP and LR in view of the areas under the receiver operating characteristic (ROC) curves (AUC).

RESULTSThe AUC of DT, MLP and LR were 0.8863, 0.8536 and 0.8802, respectively. As the larger the AUC of a specific prediction model is, the higher diagnostic ability presents, MLP performed optimally, and then followed by LR and DT in terms of 10-100 times 2-10 fold stratified cross-validation in our study. Neural network model is a preferred option for the data. However, the best subset of multiple LR would be a better choice in view of efficiency and accuracy.

CONCLUSIONWhen dealing with data from small size sample, multiple independent variables and a dichotomous outcome variable, more strategies and statistical techniques (such as AIC criteria, L-M optimization algorithm, the best subset, etc.) should be considered to build a forecast model and some available methods (such as cross-validation, AUC, etc.) could be used for evaluation.

Case-Control Studies ; Decision Trees ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Neuropathies ; diagnosis ; etiology ; Humans ; Logistic Models