A mutual regulatory loop between transcription factor Yin Yang 1 and hepatitis B virus replication influences chronic hepatitis B.

Hepatitis B virus (HBV) infections pose a major threat to human health. HBV can upregulate the expression of the transcription factor Yin Yang 1 (YY1) in in vitro cytological experiments, suggesting an association between YY1 and HBV infection. However, data on YY1 expression in chronic hepatitis B (CHB) patients are lacking. In this study, we aimed to assess the correlation between YY1 expression and HBV infection. We detected serum YY1 levels in 420 patients with chronic HBV infection, 30 patients with chronic hepatitis C virus infection, and 32 healthy controls using an enzyme-linked immunosorbent assay. The correlation between YY1 levels and clinical parameters was analyzed. Meanwhile, the changes of YY1 before and after interferon or entecavir treatment were analyzed. YY1 levels in the liver tissues were detected using immunofluorescence staining. The expression of YY1 in HBV-expressing cells was detected through western blotting. Meanwhile, we explored the effects of YY1 on HBV replication and gene expression. We found that YY1 was highly expressed in the serum and liver tissues of CHB patients. Serum YY1 levels positively correlated with HBV DNA and hepatitis B surface antigen (HBsAg). Additionally, HBV DNA levels increased but HBsAg levels decreased after HBV-expressing cells overexpress YY1. In conclusion, our study demonstrates that YY1 plays an important role in HBV replication and gene expression, providing a potential target for the treatment of CHB.

Ten cyclopentanoid monoterpenes from the whole plant of Rehmannia piasezkii maxim.

Ten new cyclopentanoid monoterpenes (1-10) were isolated from the whole plant of Rehmannia piasezkii. The structures of these compounds were elucidated based on spectroscopic data analysis. In in-vitro assays, compounds 3, 7, and 9 exhibited weak hepatoprotective activities against APAP-induced HepG2 cell damage. Compound 9 exhibited protective effect on hapassocin carbon tetrachloride model.

Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells.

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

Asiaticoside alleviates lipopolysaccharide-induced acute lung injury by blocking Sema4D/CD72 and inhibiting mitochondrial dysfunction in RAW264.7 cell and mice.

Acute lung injury (ALI) is a common disease with complex pathogenesis. However, the treatment is mainly symptomatic with limited clinical options. Asiaticoside (AS), a Chinese herbal extract, has protective effects against LPS-induced ALI in mice and inhibits nitric oxide and prostaglandin E2 synthesis; however, the specific mechanism of AS in the prevention and treatment of LPS-induced ALI needs further study. Sema4D/CD72 pathway, mitochondrial dysfunction, and miRNA-21 are closely associated with inflammation. Therefore, the present study aimed to explore whether AS exerts its therapeutic effect on ALI by influencing Sema4D/CD72 pathway and mitochondrial dysfunction, restoring the balance of inflammatory factors, and influencing miRNA-21 expression. Cell and animal experiments were performed to investigate the effect of AS on ALI. Lipopolysaccharide (LPS) was used to establish the ALI model. CCK8 and flow cytometry were used to detect the cell viability and apoptosis rate. HE staining and wet-to-dry weight ratio (W/D) of lung tissue were determined. The expressions of Sema4D, CD72, NF-κB p65, Bax, Bcl2, and caspase 3 in RAW264.7 cells and lung tissues were detected by western blot, and the levels of IL-10 and IL-1ß induced by LPS in supernatant of RAW264.7 cells and BALF were measured by ELISA. And the expression of miRNA-21 in cells and lung tissues was detected by fluorescence quantitative PCR. The result shows that AS treatment suppressed LPS-induced cell damage and lung injury in mice. AS treatment could alleviate the pathological changes such as inflammatory infiltration and histopathological changes in the lungs caused by LPS, and reduce the ratio of W/D. AS significantly alleviated the decrease of mitochondrial membrane potential induced by LPS, inhibited the increase of ROS production, and reduced the expression of mitochondrial fission proteins Drp1 and Fis1. The high-dose AS group significantly downregulated the expression of Sema4D, CD72, phosphorylated NF-κB p65, and apoptosis-related proteins, decreased the pro-inflammatory factor IL-1ß, and enhanced the level of anti-inflammatory factor IL-10. In addition, AS promoted miRNA-21 expression. These effects inhibited apoptosis and restored the balance between anti- and pro-inflammatory factors. This represents the inaugural report elucidating the mechanism by which AS inhibits the Sema4D/CD72 signaling pathway. These findings offer novel insights into the potential application of AS in both preventing and treating ALI.

Elucidating the molecular mechanisms of sepsis: Identifying key aging-related biomarkers and potential therapeutic targets in the treatment of sepsis.

BACKGROUND: Sepsis remains a crucial global health issue characterized by high mortality rates and a lack of specific treatments. This study aimed to elucidate the molecular mechanisms underlying sepsis and to identify potential therapeutic targets and compounds. METHODS: High-throughput sequencing data from the GEO database (GSE26440 as the training set and GSE13904 and GSE32707 as the validation sets), weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, alongside a combination of PPI and machine learning methods (LASSO and SVM) were utilized. RESULTS: WGCNA identified the black module as positively correlated, and the green module as negatively correlated with sepsis. Further intersections of these module genes with age-related genes yielded 57 sepsis-related genes. GO and KEGG pathway enrichment analysis, PPI, LASSO, and SVM selected six hub aging-related genes: BCL6, FOS, ETS1, ETS2, MAPK14, and MYC. A diagnostic model was constructed based on these six core genes, presenting commendable performance in both the training and validation sets. Notably, ETS1 demonstrated significant differential expression between mild and severe sepsis, indicating its potential as a biomarker of severity. Furthermore, immune infiltration analysis of these six core genes revealed their correlation with most immune cells and immune-related pathways. Additionally, compounds were identified in the traditional Chinese medicine Danshen, which upon further analysis, revealed 354 potential target proteins. GO and KEGG enrichment analysis of these targets indicated a primary enrichment in inflammation and immune-related pathways. A Venn diagram intersects these target proteins, and our aforementioned six core genes yielded three common genes, suggesting the potential efficacy of Danshen in sepsis treatment through these genes. CONCLUSIONS: This study highlights the pivotal roles of age-related genes in the molecular mechanisms of sepsis, offers potential biomarkers, and identifies promising therapeutic compounds, laying a robust foundation for future studies on the treatment of sepsis.

Electroacupuncture pretreatment mediates sympathetic nerves to alleviate myocardial ischemia-reperfusion injury via CRH neurons in the paraventricular nucleus of the hypothalamus.

BACKGROUND: Myocardial ischemia-reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia-reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. METHODS: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. RESULTS: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. CONCLUSION: EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

Structural characterization, molecular dynamic simulation, and conformational visualization of a water-soluble glucan with high molecular weight from Gastrodia elata Blume.

Polysaccharides have been widely used in the development of natural drugs and health food. However, polysaccharide characterization lags due to inherently complicated features and the limitations of existing detection approaches. We aimed to provide new insight into the fine structure and conformational visualization of polysaccharides from Gastrodia elata Blume, a medicinal and edible plant. A water-soluble polysaccharide (GEP2-6) with the high molecular weight of 2.7 × 106 Da was first obtained, and its purity reached 99.2 %. Chemical and spectroscopic analyses jointly revealed that GEP2-6 was a glucan linked by α-(1 â†’ 4) and α-(1 â†’ 6) glycosidic bonds. After enzymolysis, the local structure of GEP2-6 included α-1,4-Glcp, α-1,6-Glcp, α-1,4,6-Glcp, and α-1-Glcp at a molar ratio of 31.27∶1.32∶1.08∶0.93. The glycosidic linkage pattern of repeating units was further simulated by a glycan database and spatial examination software. The good dissolution performance was interpreted by dynamics simulation and practical molecular characteristics. Spherical flexible chains and the porous stable conformation were corroborated using atomic force microscopy. In addition, GEP2-6 could effectively scavenge DPPH and hydroxyl radicals as a promising natural antioxidant. These efforts will contribute to the expansion of clinical applications of this G. elata polysaccharide and the structural elucidation for macromolecular polysaccharides combined with traditional and modern analysis techniques.

Exogenous application of silicon and selenium improves the tolerance of tomato plants to calcium nitrate stress.

Silicon (Si) and selenium (Se) can improve the tolerance of plants to NaCl-induced salt stress. However, few studies are available on their regulatory effects on plants' tolerance to calcium nitrate stress, which often occurs in protected facilities, causing secondary soil salinization. In this study, we report the effects of Si (6 mM) and Se (20 µM) applied separately or in combination on the growth, photosynthesis, oxidative damage, and nitrogen metabolism of tomato plants, as well as fruit quality under calcium nitrate stress. The results showed that applications of Si or Se alone or in combination improved the plant growth and photosynthetic performance and reduced oxidative damage of the stressed plants. Applications of Si and Se did not decrease the calcium accumulation in leaves of the stressed plants. Under calcium nitrate stress, the concentrations of NO3-, NO2- and NH4+ in leaves were significantly increased, while the activities of nitrogen assimilation-related enzymes (including nitrate reductase, nitrite reductase, glutamine synthase, glutamine-2-oxoglutarate aminotransferase and glutamate dehydrogenase) were decreased. Applications of Si and Se, especially their combined treatment, decreased the NO3-, NO2-, and NH4+ concentrations and enhanced the activities of nitrogen assimilation-related enzymes in the stressed plants. Applied Si and Se also decreased the nitrate and titratable acid concentrations and increased vitamin levels in tomato fruits under calcium nitrate stress. It is suggested that Si and Se improved the tomato plant growth and fruit quality under calcium nitrate stress by alleviating oxidative damage and promoting both photosynthesis and nitrogen assimilation.

Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.

Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.

Hyaluronic acid-functionalized DDAB/PLGA nanoparticles for improved oral delivery of magnolol in the treatment of ulcerative colitis.

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC. The present research involved the design and preparation of a hybrid nanoparticle system (LPNs) specifically targeting macrophages at the colonic site. This was achieved by electrostatically adsorbing HA onto positively charged lipid-polymer hybrid nanoparticles (HA-LPNs). The prepared HA-LPNs exhibited a rounded morphology and a narrow size distribution. In vitro, the anti-inflammatory efficacy of Mag-HA-LPNs (which control levels of the pro-inflammatory cytokines NO, IL-6 and TNF-α) was assessed in RAW 264.7 cells. Analysis by flow cytometry and fluorescence microscopy demonstrated increased cellular uptake through HA/CD44 interaction. As expected, Mag-HA-LPNs was found to effectively increased colon length and reduced DAI scores in DSS-treated mice. This effect was achieved by regulating the inflammatory cytokines level and promoting the restoration of the colonic mucosal barrier through increased expression of Claudin-1, ZO-1 and Occludin. In this study, we developed an efficient and user-friendly delivery method for the preparation of HA-functionalized PLGA nanoparticles, which are intended for oral delivery of Mag. The findings suggest that these HA-LPNs possess the potential to serve as a promising approach for direct drug delivery to the colon for effective treatment of UC.

Glutamine Supplementation on Burn Patients: A Systematic Review and Meta-analysis.

To evaluate the effect of glutamine supplement on patients with burns, we conducted a systematic review and meta-analysis via synthesizing up-to-date studies. Databases including PubMed, Cochrane Central Register, EMBASE, Google scholar, Wanfang data, and ClinicalTrials.gov were searched up to October 2023 to find randomized trials evaluating glutamine supplement on patients with burns. The main outcomes included hospital stay, in-hospital mortality, infection, and wound healing. Twenty-two trials that randomized a total of 2170 patients were included in this meta-analysis. Pooled the length of hospital stay was shortened by glutamine supplement (weighted mean differences [WMD] = -7.95, 95% confidence interval [CI] -10.53 to -5.36, I2 = 67.9%, 16 trials). Both pooled wound healing rates (WMD = 9.15, 95% CI 6.30 to 12.01, I2 = 82.7%, 6 studies) and wound healing times (WMD = -5.84, 95% CI -7.42 to -4.27, I2 = 45.7%, 7 studies) were improved by glutamine supplement. Moreover, glutamine supplement reduced wound infection (risk ratios [RR] = 0.38, 95% CI 0.21 to 0.69, I2 = 0%, 3 trials), but not nonwound infection (RR = 0.88, 95% CI 0.73 to 1.05, I2 = 39.6%, 9 trials). Neither in-hospital mortality (RR = 0.95, 95% CI 0.74 to 1.22, I2 = 36.0%, 8 trials) nor the length of intensive care unit stay (WMD = 1.85, 95% CI -7.24 to 10.93, I2 = 78.2%, 5 studies) was improved by glutamine supplement. Subgroup analysis showed positive effects were either influenced by or based on small-scale, single-center studies. Based on the current available data, we do not recommend the routine use of glutamine supplement for burn patients in hospital. Future large-scale randomized trials are still needed to give a conclusion about the effect of glutamine supplement on burn patients.

Diagnostic Accuracy of MRI in Knee Meniscus Tear and ACL Injury.

Objective: Knee injuries are very common and may lead to other secondary injuries if effective treatment is lacking. In addition to standardized physical examination, magnetic resonance imaging (MRI) is sometimes considered an aid in the diagnosis of knee trauma. In order to have a more accurate diagnosis of knee injuries, we compared MRI with arthroscopic findings in this study to evaluate the diagnostic accuracy of MRI for meniscal tears and anterior cruciate ligament injuries of the knee. Methods: One hundred and ten patients with suspected meniscal tears and anterior cruciate ligament injuries of the knee who were admitted to our hospital from June 2020 to June 2022 were selected as study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent MRI for preoperative diagnosis, and the sensitivity, specificity, MRI findings, and confirmation of diagnosis were compared and analyzed, and the accuracy of MRI in diagnosing meniscal tears and ACL injuries of the knee was analyzed. Results: The mean ACL angle was (98.0 ± 5.4) in the MRI group and (118.0 ± 6.8) in the arthroscopic group, the difference between the two groups was statistically significant P < .05. The mean L/H value of the ACL was (2.12 ± 0.38) in the MRI group and (1.81 ± 0.19) in the arthroscopic group, which was statistically different between the two groups (P < .05). Among the patients, 68 meniscal injuries were found in the MRI examination, including 45 cases of knee meniscal tears and 23 cases of anterior cruciate ligament injuries. The sensitivity, specificity, positive and negative predictive values, agreement rate, kappa value, and Youden index of MRI in diagnosing meniscal tears and ACL injuries were all high. Conclusions: In terms of sensitivity and accuracy, MRI is an excellent imaging technique for the diagnosis of meniscal tears and anterior cruciate ligament injuries of the knee.

Engineering Scheffersomyces segobiensis for palmitoleic acid-rich lipid production.

Palmitoleic acid (POA; C16:1) is an essential high-value ω-7-conjugated fatty acid with beneficial bioactivities and potential applications in the nutraceutical and pharmaceutical industries. Previously, the oleaginous yeast Scheffersomyces segobiensis DSM27193 has been identified as a promising production host as an alternative for POA extraction from plant or animal sources. Here, the POA-producing capacity of this host was further expanded by optimizing the fermentation process and molecular strain engineering. Specifically, a dual fermentation strategy (O-S dynamic regulation strategy) focused on the substrate and dissolved oxygen concentration was designed to eliminate ethanol and pyruvate accumulation during fermentation. Key genes influencing POA production, such as jen, dgat, ole were identified on the transcriptional level and were subsequently over-expressed. Furthermore, the phosphoketolase (Xpk)/phosphotransacetylase (Pta) pathway was introduced to improve the yield of the precursor acetyl-CoA from glucose. The resulting cell factory SS-12 produced 7.3 g/L of POA, corresponding to an 11-fold increase compared to the wild type, presenting the highest POA titre reported using oleaginous yeast to date. An economic evaluation based on the raw materials, utilities and facility-dependent costs showed that microbial POA production using S. segobiensis can supersede the current extraction method from plant oil and marine fish. This study reports the construction of a promising cell factory and an effective microbial fermentation strategy for commercial POA production.

Differences in the Diagnosis and Treatment of Patients with Early-Stage Hepatocellular Liver Cancer by Multi-Row Spiral CTMDCT and Gd-EOB-DTPA-Enhanced MRI.

Objective: The assessment of liver cancer lesion characteristics mainly relies on multi-row spiral computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT suffers from a series of problems, such as low soft tissue contrast and large tumor boundary errors, which lead to its limited practical application value in liver cancer. In contrast, Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI has better soft-tissue contrast than MDCT and increases the clarity of liver cancer lesions. To investigate the differences between MDCT and Gd-EOB-DTPA-enhanced MRI in managing patients with hepatocellular liver cancer. Methods: A total of 80 patients diagnosed with hepatocellular carcinoma of the liver, who received treatment at our hospital between September 2020 and September 2022, were included in this study. These patients were evenly divided into two groups: the observation group and the control group, with 40 cases in each. The aim of this study was to compare the differences in signal indices of hepatobiliary stage between the two groups in patients with hepatocellular carcinoma. Results: A total of 89 cancer nodules were detected in patients by MDCT, and 109 cancer nodules were detected in patients by Gd-EOB-DTPA-enhanced MRI. When the number of nodules detected by both imaging modalities was statistically analyzed, the differences in the number of hepatocellular carcinoma (HCC) nodules detected by MDCT and Gd-EOB-DTPA-enhanced MRI were statistically significant (P < .05). Further analysis of the data by single cancer nodule, multiple cancer nodules, and cancer nodule size showed that the difference between the two imaging modalities was statistically significant (P < .05) in the diagnosis of patients with a single liver cancer nodule or multiple liver cancer nodules (94.8% vs.81.3%). The difference in the comparison was statistically significant (P < .05). Conclusion: Gd-EOB-DTPA-enhanced MRI demonstrates superior diagnostic efficacy in detecting small hepatocellular carcinoma, offers improved staging capabilities for hepatocellular carcinoma, and provides more precise guidance for treatment planning.Consequently, Gd-EOB-DTPA-enhanced MRI exhibits exceptional diagnostic value and serves as a valuable tool for guiding treatment decisions in patients with hepatocellular carcinoma.

Electroacupuncture prevents the development or establishment of chronic pain via IL-33/ST2 signaling in hyperalgesic priming model rats.

BACKGROUND: Chronic pain is acomplexhealth issue. Compared to acute pain, which has a protective value, chronic pain is defined as persistent pain after tissue injury. Few clinical advances have been made to prevent the transition from acute to chronic pain. Electroacupuncture (EA), the most common form of acupuncture, is widely used in clinical practice to relieve pain. METHODS: The hyperalgesic priming model, established via a carrageenan injection followed by a prostaglandin E2 injection, was used to investigate the development or establishment of chronic pain. We observed the hyperalgesic effect of EA on rats and investigated the expression p38 mitogen-activated protein kinase, interleukin-33 (IL-33), and its receptor ST2 in astrocytes in the L4-L6 spinal cord dorsal horns (SDHs) after EA. The IL-33/ST2 signaling pathway in SDH is associated with the development of chronic pain. RESULTS: EA can reverse the pain threshold in hyperalgesic priming model rats and regulates the expression of phosphorylated p38, IL-33, and ST2 in astrocytes in the L4-L6 SDHs. We discovered that EA raises the pain threshold. This suggests that EA can prevent the development or establishment of chronic pain by inhibiting IL-33/ST2 signaling in the lower central nervous system. CONCLUSIONS: EA can alleviate the development or establishment of chronic pain by modulating IL-33/ST2 signaling in SDHs. Our findings will help clinicians understand the mechanisms of EA analgesia.

Transcutaneous electrical acupoint stimulation for cancer-related pain management in patients receiving chronic opioid therapy: a randomized clinical trial.

PURPOSE: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. METHODS: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. RESULTS: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). CONCLUSIONS: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. CLINICALTRIAL: GOV: ChiCTR-TRC-13003803.

Distribution of and Temporal Variation in Volatiles in Tea (Camellia sinensis) Flowers during the Opening Stages.

Tea (Camellia sinensis) flowers emit a large amount of volatiles that attract pollinators. However, few studies have characterized temporal and spatial variation in tea floral volatiles. To investigate the distribution of volatiles within tea flowers and their variation among opening stages, volatile components from different parts of tea flowers and different opening stages were collected by headspace solid-phase microextraction and analyzed by gas chromatography-mass spectrometry. A total of 51 volatile compounds of eight chemical classes were identified in the tea flowers. Volatile compounds were most abundant in tea flowers of the Shuchazao cultivar. Acetophenone, 1-phenylethanol, 2-phenylethanol, and benzyl alcohol were the most abundant volatiles. Terpenes were common in the sepals, and benzoids were common in the stamens. The fatty acid derivatives were mainly distributed in the pistils and receptacles and were less abundant in the petals, sepals, and stamens. During the opening phase of tea flowers, the volatile content increased 12-fold, which mainly stemmed from the increase in benzoids. These results enhance our understanding of the formation of volatiles in tea flowers.

A New Target of Electroacupuncture Pretreatment Mediated Sympathetic Nervous to Improve MIRI: Glutamatergic Neurons in Fastigial Nucleus of the Cerebellum.

Ischemic heart disease is a fatal cardiovascular disease that irreversibly impairs the function of the heart, followed by reperfusion leading to a further increase in infarct size. Clinically, we call it myocardial ischemia-reperfusion injury (MIRI). A growing number of clinical observations and experimental studies have found electroacupuncture (EA) to be effective in alleviating MIRI. This study attempts to investigate whether glutamatergic neurons in fastigial nucleus (FN) of the cerebellum are involved in EA pretreatment to alleviate MIRI via sympathetic nerves, and the potential mechanisms of EA pretreatment process. A MIRI model was established by ligating the coronary artery of the left anterior descending branch of the heart for 30 minutes, followed by 2 hours of reperfusion. Multichannel physiological recordings, electrocardiogram, cardiac ultrasound, chemical genetics, enzyme-linked immunosorbent assay and immunofluorescence staining methods were combined to demonstrate that EA pretreatment inhibited neuronal firing and c-Fos expression in FN of the cerebellum and reduced cardiac sympathetic firing. Meanwhile, EA pretreatment significantly reduced cardiac ejection fraction (EF), shortening fraction (SF), percentage infarct area, decreased myocardial norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) concentrations, and improved MIRI-induced myocardial tissue morphology. The results were similar to the inhibition of glutamatergic neurons in FN. However, the activation of glutamatergic neurons in FN diminished the aforementioned effects of EA pretreatment. This study revealed that glutamatergic neurons in FN of the cerebellum is involved in EA pretreatment mediated sympathetic nervous and may be a potential mediator for improving MIRI.