Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To explore the functional rehabilitation of patients with rheumatoid arthritis (RA) after total knee arthroplasty (TKA). METHODS: A retrospective analysis was conducted on 101 patients who needed TKA due to rheumatoid arthritis (RA) involving both knees from January 2017 to December 2020, including 16 males and 85 females, aged from 41 to 65 years old with an average of (58.13±5.53) years old;body mass index (BMI) ranged from 16.88 to 33.33 kg·m^-2 with an average of (23.16±3.49) kg·m^-2;63 patients with grade 1, 29 patients with grade 2, and 9 patients with grade 3 according to classification of American Society of Anesthesiologists (ASA). According to the latest follow-up results at 12 months after operation, 82 patients returned to work and 19 patients did not return to work. Visual analogue scale(VAS) was used to evaluate the degree of pain relief before operation and 12 months after operation, and work, osteoarthritis and joint replacement questionnaire (WORQ) was used to evaluate knee joint activity status of all patients before and after operation, and the working ability index was used to evaluate working ability of all patients before operation and 12 months after operation. For the 82 patients who returned to work, the labor time stopped before operation and within 12 months after operation was compared, and the changes in labor grades, types of work and labor hours of patients before and after operation were recorded. For the 19 patients who did not return to work, the specific reasons for their non-return to work was analyzed;the postoperative satisfaction of patients was evaluated by using Likert satisfaction scale. All patients were followed up for at least 12 months. VAS was decreased from (6.49±0.59) before operation to (1.10±0.43) at 12 months after operation (P<0.05);for WORQ questionnaire survey, scores of walking, sitting posture, standing and stair climbing were increased from (1.07±0.35), (1.05±0.29), (1.06±0.34) and (1.14±0.42) before operation to (3.00±0.00), (2.87±0.33), (2.95±0.21) and (2.95±0.21) after operation, respectively, had statistically significant (P<0.05);the labor work index of all patients increased from 1.11±0.46 before operation to 2.99±0.10 at 12 months after operation, and the difference was statistically significant (P<0.05). Among the 82 patients who returned to work after operation, regarding the time of stopping labor, 81 patients stopped working within 3 months before operation, 1 patient stopped working for 4 to 6 months after operation, and the number of patients who stopped working was 81, 1, and 0 respectively. Forty patients returned to work within 3 months after operation, 4 to 6 months after operation for 29 patients, and 12 months after operation for 13 patients. 95.1% (78/82) of patients engaged in light labor before operation, and 85.4% (70/82) of patients engaged in moderate labor after operation. At 12 months after operation, the types of jobs and working hours available to all patients increased compared with those before operation. Among 19 patients who did not return to work after TKA, 7 patients had poor control of rheumatoid arthritis, 5 patients still felt pain, swelling and numbness on knee joint, 2 patients had retired, and 5 patients had other reasons. Eighty-six patients (85%) expressed great satisfaction with the postoperative working ability, 8 patients (8%) expressed satisfaction with the postoperative working ability, 6 patients (6%) expressed acceptance of postoperative working ability, and 1 patient (1%) expressed dissatisfaction with postoperative working ability. CONCLUSION TKA is an effective treatment option for patients with RA. After undergoing TKA, patients could significantly improve pain and functional activities of knee joint, and effectively enhance the quality of life and working ability. For patients whose rehabilitation labor capacity is not fully met, postoperative management and personalized rehabilitation treatment need to be strengthened to achieve the best rehabilitation effect.
Humans ; Female ; Male ; Arthroplasty, Replacement, Knee/rehabilitation* ; Arthritis, Rheumatoid/physiopathology* ; Middle Aged ; Aged ; Retrospective Studies ; Adult

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.
Humans ; Anesthesia, General ; Brain/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine/physiology* ; Animals

The anti-counterfeiting application of three-color fluorescent carbon dots(CDs)in high-quality inkjet printing was studied.Blue,green and red fluorescent CDs were synthesized by solvothermal method using three kinds of isomers of phenylenediamine as precursor,and ethanol-glycerol mixture as solvent.The morphology,composition,structure,and optical properties were characterized.Blue,green and red fluorescent inks were then prepared by diluting CDs with water.The dilution ratio,excitation light source and filtering method were also optimized.The optimal dilution ratio of blue,green and red fluorescent ink was 5,5 and 20,respectively.Under 365,415 and 450 nm light excitation,bright blue,green and red fluorescence from above inks could be observed by using a blue,green and red filter,respectively.These fluorescent inks were finally used for high-quality inkjet printing through monochrome printing mode and polychrome printing mode.In addition,the sensitivity and contrast of printing were quantitatively investigated.The series of three-color fluorescent inks possessed great prospects in ordinary and invisible fluorescent anti-counterfeiting application.

Objective To investigate the predictive value of atherosclerotic index of plasma(AIP)for the risk of coronary heart disease(CHD)in patients with nonalcoholic fatty liver disease(NAFLD).Methods A retrospective analysis was conducted in 299 patients with NAFLD.Based on presence or absence of CHD,the patients were divided into NAFLD with CHD group(n=177)and NAFLD group(n=122).Clinical data were collected from both groups,and AIP was calculat-ed.Multivariate Logistic regression analysis was performed to explore the independent risk factors for CHD in patients with NAFLD.Receiver operating characteristic(ROC)curves were plotted to evalu-ate the predictive value of AIP for the risk of CHD in patients with NAFLD.Results The NAFLD with CHD group had a higher proportion of males,smokers,and higher levels of alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),fasting plasma glucose(FPG),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),γ-glutamyltransferase(GGT),uric acid(UA),and AIP than the NAFLD group.The NAFLD with CHD group also had lower levels of high-density lipoprotein cholesterol(HDL-C)than the NAFLD group(P＜0.05).Multivariate Logistic regression analysis revealed that males(OR=2.548,95％CI,1.402 to 4.632,P=0.002),high levels of AST(OR=1.038,95％CI,1.002 to 1.077,P=0.041),high levels of LDL-C(OR=1.811,95％CI,1.242 to 2.640,P=0.002),and high AIP(OR=16.117,95％CI,1.874 to 138.609,P=0.011)were independent risk factors for CHD in patients with NAFLD(P＜0.05).ROC curve analysis showed that AIP had an area under the curve of 0.746(95％CI,0.688 to 0.804)for pre-dicting CHD in patients with NAFLD,with a sensitivity of 76.3％and a specificity of 73.0％.Conclusion AIP is an independent influencing factor for CHD in patients with NAFLD and has certain predictive value for the risk of CHD in these patients.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.