Objective:To investigate associations of cerebral perfusion impairment with early neurological deterioration (END) and poor outcome in patients with acute small subcortical infarction (SSI).Methods:Patients with SSI in the perforator artery region admitted to the Department of Neurology, Zhengzhou People's Hospital between January 2020 and November 2022 were prospectively included. END was defined as an increase of ≥2 in the total score of the National Institutes of Health Stroke Scale (NIHSS) or an increase of ≥1 in the motor function score within 72 h after admission. Poor outcome was defined as the modified Rankin Scale score of 2 at 90 d after onset. Cerebral perfusion impairment was defined according to MRI perfusion-weighted imaging parameters. The demographic, baseline clinical and imaging data were collected. Multivariate logistic regression analysis was used to determine associations of cerebral perfusion impairment and END and poor outcome in patients with SSI. Results:A total of 100 patients with SSI were enrolled, including 56 males (56.0%), and aged 69.2±5.8 years. Among them, 19 patients (19.0%) developed END, 27 (27.0%) had poor outcome, and 51 (51.0%) had significant cerebral perfusion impairment. There were statistically significant differences in high sensitivity C-reactive protein, white matter hyperintensities (WMHs) in the basal ganglia, enlarged perivascular space (EPVS) in the basal ganglia, deep cerebral microbleeds (CMBs), and cerebral perfusion impairment between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that higher diastolic blood pressure (odds ratio [ OR] 1.070, 95% confidence interval [ CI] 1.003-1.141); P=0.040], deep WMHs ( OR 2.271, 95% CI 1.135-4.544; P=0.020), deep CMBs ( OR 5.047, 95% CI 1.240-20.549; P=0.024), and cerebral perfusion impairment ( OR 6.083, 95% CI 1.318-28.080; P=0.021) were independent risk factors for END in patients with SSI. There were statistically significant differences in hypersensitive C-reactive protein, NIHSS score at END, basal ganglia EPVS, END, and cerebral perfusion impairment between the poor outcome group and the good outcome group ( P<0.05). Multivariate logistic regression analysis showed that NIHSS score at END ( OR 1.485, 95% CI 1.034-2.133; P=0.032), basal ganglia EPVS ( OR 3.005, 95% CI 1.224-7.378; P=0.016), and cerebral perfusion impairment ( OR 9.234, 95% CI 1.994-42.765; P=0.004) were independent risk factors for the poor outcome at 90 d in patients with SSI, while anterior circulation infarction ( OR 0.066, 95% CI 0.013-0.334; P=0.001) was independently negatively correlated with the poor outcomes at 90 d after onset. Conclusion:Cerebral perfusion impairment is an independent risk factor for END and poor outcome at 90 d after onset in patients with SSI.

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

An innovative approach to quantitatively analyze the histamine and its precursor histidine simultaneously in biological matrices was established for the first time based on double adsorption combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).The internal standard was 2-dihydroxybenzoic acid (DHB).The plasma and brain tissue homogenate was protein precipitated with 3-fold acetonitrile, and the supernatant was then sampled for injection analysis.The chromatographic separation of the target components was achieved on an amino chromatography column (ODS-SPXBridge? Amide).Gradient elution was carried out with the mobile phase consisting of solvent A (0.1% formic acid and 1mmol/L ammonium formate in water) and solvent B (acetonitrile).Mass spectrometry was employed for quantitative analysis with ESI ion source in multiple reaction monitoring (MRM) mode.In order to improve the specificity and accuracy, activated carbon and calcite were used for the double adsorption of biological matrices for the first time.The adsorbed matrix was then used for methodology validation.The results showed that histamine and histidine were linear in the quantitative range (correlation coefficient r ≥ 0.999).Accuracy, precision, extraction recovery, matrix effect and stability all met the requirements of biological sample analysis.All results suggested that the present method could not only be efficiently and reliably used for simultaneous quantitative analysis of histamine and histidine in biological samples, but also provide reference for the detection of other endogenous substances.

Objective:To explore the efficacy and safety of neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients.Methods:Six patients with NSCLC who were diagnosed as ⅢA and received two cycles of neoadjuvant chemoimmunotherapy and surgery between September 2019 and January 2020 were described in this study.Results:Five of them experienced AEs during neoadjuvant therapy. All of them received surgery and achieved an MPR of 50%. No viable tumor cells were found in the tissues of one patient. One patient with a small bronchopleural fistula after lobectomy.Conclusion:Neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients is safe and efficient. Long-term outcomes of neoadjuvant chemoimmunotherapy combined with surgery should be further validated.

As a low-load physiological monitoring technology, wearable devices can provide new methods for monitoring, evaluating and managing chronic diseases, which is a direction for the future development of monitoring technology. However, as a new type of monitoring technology, its clinical application mode and value are still unclear and need to be further explored. In this study, a central monitoring system based on wearable devices was built in the general ward (non-ICU ward) of PLA General Hospital, the value points of clinical application of wearable physiological monitoring technology were analyzed, and the system was combined with the treatment process and applied to clinical monitoring. The system is able to effectively collect data such as electrocardiogram, respiration, blood oxygen, pulse rate, and body position/movement to achieve real-time monitoring, prediction and early warning, and condition assessment. And since its operation from March 2018, 1 268 people (657 patients) have undergone wearable continuous physiological monitoring until January 2020, with data from a total of 1 198 people (632 cases) screened for signals through signal quality algorithms and manual interpretation were available for analysis, accounting for 94.48 % (96.19%) of the total. Through continuous physiological data analysis and manual correction, sleep apnea event, nocturnal hypoxemia, tachycardia, and ventricular premature beats were detected in 232 (36.65%), 58 (9.16%), 30 (4.74%), and 42 (6.64%) of the total patients, while the number of these abnormal events recorded in the archives was 4 (0.63%), 0 (0.00%), 24 (3.80%), and 15 (2.37%) cases. The statistical analysis of sleep apnea event outcomes revealed that patients with chronic diseases were more likely to have sleep apnea events than healthy individuals, and the incidence was higher in men (62.93%) than in women (37.07%). The results indicate that wearable physiological monitoring technology can provide a new monitoring mode for inpatients, capturing more abnormal events and provide richer information for clinical diagnosis and treatment through continuous physiological parameter analysis, and can be effectively integrated into existing medical processes. We will continue to explore the applicability of this new monitoring mode in different clinical scenarios to further enrich the clinical application of wearable technology and provide richer tools and methods for the monitoring, evaluation and management of chronic diseases.
Heart Rate ; Humans ; Monitoring, Physiologic ; Movement ; Sleep Apnea Syndromes ; Wearable Electronic Devices

【Objective】 To analyze the data of non-small cell lung cancer (NSCLC) gene chip using the bioinformatics method, screen differential expression genes (DEGs), and explore the biomarkers related to the prognosis of NSCLC so as to provide a new target for the treatment of NSCLC. 【Methods】 The NSCLC gene chip data were downloaded from the GEO database and the common DEGs in the two datasets were screened by GEO2R tool and FunRich3.1.3 software. The DAVID database was used in GO analysis and KEGG analysis of the DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database; Cytoscape 3.8.0 software was used to select the top 20 hub genes. Then Kaplan-Meier plotter was used to analyze the prognosis of the identified hub genes, and multiple external databases were used to verify the expressions of the hub genes and their relationship with prognosis. 【Results】 A total of 159 intersect DEGs were screened from the two datasets. A total of 20 hub genes were identified via PPI network. Survival analysis and validation results from multiple external databases showed that SPP1 was highly expressed in NSCLC tumor tissues and was significantly correlated with the patients’ poor prognosis (P<0.05). The subgroup analysis showed that SPP1 might cause the poor prognosis by affecting lymph node metastasis. 【Conclusion】 SPP1 may be a biomarker for evaluating the prognosis of NSCLC patients, providing a new idea for the targeted therapy of NSCLC.

Objective:To investigate the risk factors for hemorrhagic transformation (HT) in patients with acute posterior circulation ischemic stroke (PCIS) and its impact on outcomes.Methods:From July 2016 to October 2019, patients admitted to the Department of Neurology, the People's Hospital of Zhengzhou and diagnosed as PCIS were enrolled retrospectively. Their demography, clinical data, laboratory and imaging findings were collected. HT was defined as no intracranial hemorrhage detected by the first head CT/MRI after onset, and intracranial hemorrhage was found during head CT/MRI reexamination within 10 d after onset. Symptomatic HT was defined as intracranial hemorrhage indicated by imaging reexamination and the National Institutes of Health Stroke Scale (NIHSS) score was higher than the baseline. The outcome was evaluated by the modified Rankin Scale at 3 months after onset, and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for HT, symptomatic HT, and poor outcomes. Results:A total of 242 patients with PCIS were enrolled. Their age was 68.02±12.0 years, and 111 were females (45.9%). The baseline median NIHSS score was 5.9 (interquartile range: 3.1-8.8). HT occurred in 19 patients (7.9%), and 14 of them (73.7%) were symptomatic HT. Follow-up at 3 months showed that 74 patients (30.58%) had poor outcomes, of which 12 died. Multivariate logistic regression analysis showed that higher baseline systolic blood pressure (odds ratio [ OR] 1.076, 95% confidence interval [ CI] 1.021-1.135, P=0.006; OR 1.161, 95% CI 1.087-1.240, P<0.001) and larger infarct volume ( OR 31.293, 95% CI 4.542-215.592, P<0.001; OR 2.084, 95% CI 1.414-3.073, P<0.001) were the independent risk factors for HT and symptomatic HT. The higher NIHSS score ( OR 1.511, 95% CI 1.307-1.746; P<0.001), diabetes mellitus ( OR 2.041, 95% CI 1.054-3.952; P=0.034) and symptomatic HT ( OR 4.514, 95% CI 1.458-13.979; P=0.009) were the independent risk factors for poor outcomes. Conclusions:HT is rare in patients with PCIS. Higher baseline systolic blood pressure and larger infarct volume are the independent risk factors for HT in patients with PCIS. Higher baseline NIHSS scores, diabetes mellitus, and symptomatic HT are the independent risk factors for poor outcomes in patients with PCIS.

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

Objective:To investigate the short-term effects of articular injection of hyaluronic acid combined with glucocorticoid in patients with knee osteoarthritis.Methods:From October 2017 to June 2018, a total of 188 patients diagnosed with knee osteoarthritis received parallel articular injection. There were 60 cases with mild knee osteoarthritis, 72 with moderate and 56 with severe according to the WOMAC knee functional score. There patients were divided into group rank Ⅰ48 cases, Ⅱ 49 cases, Ⅲ 45 cases, Ⅳ 46 cases according to the knee joint X-ray Kellgren-Lawrence classification. The unified treatment regimen was 2.5 ml Sodium Hyaluronate (SHA) injection for the first time, SHA 2.5 ml and compound betamethasone injection (CBI) 1 ml for the second week, and 2.5 ml of SHA for the third week. WOMAC score and Lequesne index were used to evaluate joint function before the first injection and after SHA and SHA+CBI injection. The improvement rate of Lequesne index ≥30% or improvement rate of WOMAC score ≥25% was regarded as effective treatment.Results:Lequesne index and WOMAC score decreased gradually in the mild, moderate and severe groups after 3 weeks of injection. Among these patients, the improvement rates of Lequesne index after SHA injection and SHA+CBI injection were 36.44%±8.46% and 49.26%±13.75% in the mild group, 23.09%±12.61% and 30.66%±14.95% in the moderate group, and 10.50%±8.78% and 11.07%±6.52% in the severe group. The improvement rate of WOMAC score in the mild group after SHA injection and after SHA+CBI injection was greater than 25%. After SHA injection, the improvement rate of WOMAC score was 13.06%±10.21% in the moderate group, and 27.49%±13.61% after SHA+CBI injection. Those in severe group were all less than 25%. Kendall's staub correlation analysis results showed that there was a strong positive correlation between WOMAC function score and X-ray Kellgren-Lawrence classification ( r=0.744, P<0.001). The Lequesne index and WOMAC scores of the Kellgren-Lawrence X-ray classification decreased gradually after 3 weeks of injection. The improvement rate of Lequesne index period in group rank Ⅰ after SHA and SHA+CBI injection was 36.64%±10.05% and 52.00%±8.19%, respectively. That for group rank Ⅱ was 32.05%±8.09% and 41.95%±10.53%, group rank Ⅲ 16.93%±10.34% and 27.77%±10.25%, group rank Ⅳ 7.52%±5.53% and 7.60%±6.66%. The improvement rate of WOMAC score period in group rank Ⅰ after SHA and SHA+CBI injection was 29.48%±11.77% and 42.59%±13.55%, respectively. That for group rank Ⅱ was 26.72%±10.21% and 30.49%±16.90%, group rank Ⅲ 13.78%±5.96% and 23.05%±9.52%, group rank Ⅳ 4.77%±3.80% and 4.27%±4.23%. Conclusion:For mild or X-ray classification Ⅰ, Ⅱ knee osteoarthritis patients, articular injection SHA or SHA+CBI are effective. Further, SHA+CBI is better than single injection of SHA. SHA+CBI injection was effective for moderate knee osteoarthritis patients. For severe or X-ray classification Ⅲ, Ⅳ patients, SHA or SHA+CBI injection at interval are invalid.