BACKGROUND:Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels;however,the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear. OBJECTIVE:To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method. METHODS:Five features associated with behavioral correlations in the Oswestry disability index score,including time spent watching TV,time spent on the computer,and light/moderate/vigorous physical activity,were selected from large-scale population-based genome-wide association studies,and instrumental variables were extracted for each of these behaviorally related features.Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database.The results were analyzed using the inverse variance weighted,MR-Egger regression,simple mode,weighted mode,weighted median estimator,and regression model odds ratios(OR)and 95%confidence interval(CI)to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration.Cochran's Q was used to test for heterogeneity,MR-Egger intercept to test for multiplicity,and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration. RESULTS AND CONCLUSION:The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration(OR=1.775,95%CI:1.418-2.221,P<0.001)/(OR=1.384,95%CI:1.041-1.839,P<0.001),an inverse causal association between light physical activity and the risk of intervertebral disc degeneration(OR=1.000,95%CI:0.999-1.000,P=0.020).MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration(P=0.005),while there was no horizontal pleiotropy between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=0.521,P=0.851).Cochran's Q analysis showed that heterogeneity was observed between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=3.33×10-11,P=0.001),and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration(P=0.186).Overall,there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration,i.e.,not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score,but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration.These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration,indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration,and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.

Objective: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. Methods: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated. Results: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. Conclusion NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Objective: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. Methods: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated. Results: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. Conclusion NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Objective: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. Methods: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated. Results: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. Conclusion NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

OBJECTIVE: To accurately measure human energy metabolism with high temporal resolution, a respiratory gas analysis system was designed using a breath-by-breath approach. METHODS: Firstly, indirect calorimetry was employed in respiratory gas analysis to measure the respiratory flow and concentration signals in real-time. Secondly, oxygen consumption QO2 and carbon dioxide production QCO2 were calculated through respiratory characteristic alignment and respiratory signal segmentation. Finally, metabolic indexes were calculated according to the Weir formula. Furthermore, a controlled trial was formulated for validation comparisons with the MGC ULTIMA SYSTEM PFX CARDIO2. RESULTS: The results indicate that the data points of metabolic indexes measured by this system all fall within the confidence interval when compared with those of the MGC. CONCLUSION The system has high consistency with the MGC measurement results. Thus, the system can accurately measure metabolism in real-time and provide data support for clinical nutrition assessment and therapy.
Humans ; Energy Metabolism ; Breath Tests/instrumentation* ; Calorimetry, Indirect/instrumentation* ; Equipment Design

Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

The biliary microbiota is an important component of the biliary system, the structure changes and dysbiosis of the biliary microbiota are closely related to the occurrence and development of biliary diseases. Recent studies have found that the dysbiosis of the biliary microbiota can lead to the occurrence of various biliary diseases such as cholelithiasis, cholangitis, and biliary tract cancer. However, the specific mechanisms of some of these diseases remain unclear. In addition, the alternation of biliary microbiota may also lead to the occurrence of postoperative complications of biliary diseases, such as the risk of infection increased after laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP). Although some studies have begun to explore the connection between biliary microbiota and biliary diseases, most research have mainly focused on a single disease type or specific microorganisms. There has been no comprehensive and systematic review of the overall changes in biliary microbiota across different diseases and their association with post biliary surgery infection.Therefore, this article presents a systematic review of current advances linking the alternations of biliary microbiota to the development of biliary diseases and their postoperative infections, as well as the changes in the biliary microbiota before and after various biliary diseases and their surgeries, aiming to provide insightful methods for the early diagnosis, prevention and treatment of biliary diseases and management of postoperative infections.

Objective : To explore the adverse effects of mild traumatic brain injury ( MTBI) on the memory monito- ring function of patients． Methods : This study adopted a paired control research method，combined neuropsycho- logical background tests and memory monitoring task ( feeling of knowing，FOK) to conduct cognitive assessments on two groups of subjects: the patient group ( n = 42) and the matched control group ( n = 42) ． Results : In neuropsychological background test，the patients' performance in digit span test，Stroop color task，digit link task and auditory verbal learning test were significantly lower than those in the control group ( P＜0. 05) ．In addition，there was significant difference in accuracy of FOK task between the two groups ( P ＜0. 05) ．The ratio of right judge- ment / right recognition was relatively high in the control group，while the ratio of correct judgement /wrong recogni- tion was relatively high in the patient group． Conclusion This study confirms that memory impairment in MTBI patients is centered on damage to memory monitoring function．Moreover，the damage to attention，execution，and item content memory abilities in MTBI patients are important driving factors for their memory monitoring dysfunction．

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.