ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
Humans ; Adult ; Hepatitis B, Chronic/complications* ; Retrospective Studies ; Cross-Sectional Studies ; Hepatitis B e Antigens ; DNA, Viral ; Antiviral Agents/therapeutic use* ; Hepatitis B virus/genetics* ; Demography

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Objective:To explore the postprandial plasma low-density lipoprotein cholesterol (LDL-C) changes by various detection methods.Methods:A total of 85 subjects admitted to the Second Xiangya Hospital of Central South University from November 2017 to May 2019 were included. Serum samples were collected from fasting and the 2 nd hour and the 4 th hour after breakfast. Serum lipid levels were measured with enzymatic assays and nuclear magnetic resonance spectroscopy (NMRS), and proprotein invertase subtilisin/kexin type 9 (PCSK9) levels were measured with enzyme-linked immunosorbent assays. The differences of blood lipid components at different time points were compared by Friedman two-way rank analysis of variance and Wilcoxon signed rank test, and the correlation between PCSK9 level and lipoprotein particles was analyzed by Spearman correlation. Results:Measured by enzymatic assays, compared with the fasting state, LDL-C decreased at the 2 nd hour and the 4 th hour after the meal (2.58[2.09, 3.12], 2.47[1.92, 3.02], 2.37[1.82, 2.80] mmol/L, P<0.001). Measured by NMRS, the concentration of LDL particles (1 086[830, 1 239], 1 083[848, 1 213], 1 061[814, 1 213] nmol/L, P=0.417) did not change significantly, and cholesterol in LDL particles were 2.13 (1.56, 2.54), 2.16 (1.68, 2.50), 2.06 (1.58, 2.50) mmol/L, respectively ( P=0.047)，and postprandial cholesterol in LDL particles in the 2 nd hour and in the 4 th hour did not change significantly compared with fasting ( P>0.05). while the concentration of large LDL particles (185.2[150.6,221.6], 173.0[144.8,220.3], 178.1[144.0,233.6] nmol/L, P=0.001), and the cholesterol level in large LDL particles (0.49[0.39, 0.57], 0.47[0.38, 0.57], 0.46[0.37, 0.58]mmol/L, P<0.001) decreased after the meal. The PCSK9 level also decreased significantly after the meal (299[233, 397], 257[208, 342], 251[215, 340] ng/ml, P<0.001). There was an independent positive correlation between the decrease of PCSK9 levels and the increase of remnant cholesterol detected by MNRS after the meal ( r=0.232, P=0.035). Conclusions:The postprandial LDL-C level measured by NMRS and enzymatic assays is not consistent. The decrease of LDL-C measured by enzymatic assays is not caused by the clearance of LDL particles, but by the redistribution of cholesterol in each LDL subfraction.

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Objective:To investigate the effect and mechanism of Fuzheng Touxie prescription （FZTX） on the immune homeostasis of drug-resistant Pseudomonas aeruginosa lung infection in rats at different time points. Method:A total of 168 rats were divided into a blank group （n=8），a model group （n=40），a Touxie （TX） group （n=40），an early Fuzheng （FZ） group （n=40）， and a delayed FZ group （n=40）. The blank group was given distilled water by gavage， the model group was given distilled water by gavage after infection，the TX group was given clear heat and penetrate evil drug free decoction granules（3.5 g·kg^-1） by gavage after infection， the early FZ group was given Fuzheng Touxie whole formula free decoction granules（10.75 g·kg^-1） by gavage after infection， the delayed FZ group was given clear heat and penetrate evil drug free decoction granules by gavage after infection， on the third day plus Fuzheng drug free decoction granules［（3.5+10.75） g·kg^-1］ by gavage， the three treatment groups were gavaged twice a day， 2 mL each time .Each drug treatment group was divided into five groups according to five time points （3 h，1 d，3 d，5 d， and 7 d）， with eight rats in each group. The levels of tumor necrosis factor-α（TNF-α），high mobility group protein 1（HMGB1），interleukin-10（IL-10）， and tumor necrosis factor -α-induced protein-8-like2 （TIPE2） were measured by enzyme-linked immunosorbent assay （ELISA）， and HMGB1 protein expression level by Western blot. Result:At 3 h，the TNF-α content in the drug treatment groups was higher than that in the blank group and the model group （P<0.05）. At 3 d，the TNF-α content in the early FZ group and the delayed FZ group was lower than that in the model group （P<0.05） and the TX group （P<0.05）. At 1 d，the HMGB1 content in the TX group and the delayed FZ group was higher than that in the model group （P<0.05）. At 5 d，the HMGB1 content was lower in the delayed FZ group than in the model group （P<0.05）. At 7 d，HMGB1 protein expression in the model group was higher than that in the blank group （P<0.05） and the early FZ group （P<0.05）. At 3 d，the IL-10 content was significantly higher in both the early FZ group and the delayed FZ group than that in the model group （P<0.05）. At 5 d，the IL-10 content was higher in the early FZ group than that in the TX group （P<0.05）. At 7 d，the IL-10 content in the early FZ group and the delayed FZ group was lower than that in the TX group （P<0.05）. At 5 d，the TIPE2 content in the early FZ group was lower than that in the model group （P<0.05）. At 7 d，the TIPE2 content in the TX group and the delayed FZ group was lower than that in the model group （P<0.05）. Conclusion:FZTX or modified prescription can promote the inflammatory response to eliminate pathogenic bacteria in the early stage and suppress the inflammatory response in the late stage to avoid the inflammatory cascade effect and lung tissue damage，indicating that Fuzheng drugs have an important role in maintaining the immune homeostasis of the body after infection.

Objective:To study the protective effect of essential oil from Alpiniae Zerumbet Fructus （EOAZF） against high glucose （HG）-induced injury of human umbilical vein endothelial cells （HUVECs） in vitro， so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF. Method:The cells were divided into the normal group， model group （25 mmol·L^-1 glucose）， positive control group （100 mg·L^-1 vitamin C）， and the low- （0.25 μg·L^-1）， medium- （1 μg·L^-1）， and high-dose （4 μg·L^-1） EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde （MDA）， nitric oxide （NO）， and endothelin-1 （ET-1） in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species （ROS） generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） staining and dichloro-dihydro-fluorescein diacetate （DCFH-DA） assay. The protein and mRNA expression levels of thioredoxin interacting protein （TXNIP） and thioredoxin 1 （Trx-1） were determined by Western blot and Real-time polymerase chain reaction （Real-time PCR）， followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method. Result:The comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group， EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 （P<0.05） in the model group were increased in contrast to those in the control group， while the NO level was decreased （P<0.01）. Compared with the model group， EOAZF at all the three concentrations， especially at 4 μg·L^-1， obviously reduced the secretion of MDA and ET-1 （P<0.05）， but elevated NO after HG induction （P<0.05）. The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group （P<0.01）. Compared with the model group， EOAZF at 4 μg·L^-1 significantly lowered the ROS level and apoptosis （P<0.05） of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group （P<0.05）， whereas the Trx-1 activity was decreased （P<0.01）. Compared with the model group， EOAZF at 4 μg·L^-1 significantly down-regulated the mRNA and protein （P<0.05） expression levels of TXNIP and enhanced the total Trx-1 activity （P<0.05） in HUVECs， thus suppressing the oxidative stress. Conclusion:EOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.

OBJECTIVE: To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers. METHODS: "GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs. RESULTS: A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships. CONCLUSION The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.
Biomarkers, Tumor/genetics* ; Early Detection of Cancer ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics* ; Neoplasms/genetics* ; Prognosis

Objective: To investigate the predictive value of N-terminal type B natriuretic peptide（NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure（non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction（LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group （<125 ng/L) and high NT-proBNP group（≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was （74.9±6.5) years, including 304（50.7%) males. The median follow-up time was 344（265, 359) days. One hundred and seventy-eight（29.7%) composite endpoint events were recorded during the follow-up, 19（3.2%) patients died, and 12（2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases（52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group（all P<0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group（33.4%（105/314) vs. 24.8%（71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group（17.5%（55/314) vs. 8.4%（24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events（Log-rank P=0.016) and cardiovascular events（Log-rank P=0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group（4.8%（15/314) vs. 1.4%（4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance（Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events（HR=1.376，95%CI 1.049-1.806, P=0.021), and cardiovascular events（HR=1.777, 95%CI 1.185-2.664, P=0.005), but not for all-cause mortality（P=0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.
Aged ; Aged, 80 and over ; Biomarkers ; Heart Failure ; Humans ; Male ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Stroke Volume ; Ventricular Function, Left