[Bupleuri Radix-Paeoniae Radix Alba medicated plasma exerts effects on HepG2 hepatoma cells by regulating miR-1297/PTEN signaling axis].

The present study aimed to investigate the effect and mechanism of Bupleuri Radix-Paeoniae Radix Alba medicated plasma on HepG2 hepatoma cells by regulating the microRNA-1297(miR-1297)/phosphatase and tensin homologue deleted on chromosome 10(PTEN) signaling axis. Real-time quantitative PCR(RT-qPCR) was carried out to determine the mRNA levels of miR-1297 and PTEN in different hepatoma cell lines. The dual luciferase reporter assay was employed to verify the targeted interaction between miR-1297 and PTEN. The cell counting kit-8(CCK-8) was used to detect cell proliferation, and the optimal concentration and intervention time of the medicated plasma were determined. The cell invasion and migration were examined by Transwell assay and wound healing assay. Cell cycle distribution was detected by PI staining, and the apoptosis of cells was detected by Annexin V-FITC/PI double staining. The mRNA levels of miR-1297, PTEN, protein kinase B(Akt), and phosphatidylinositol 3-kinase(PI3K) were determined by RT-qPCR. Western blot was employed to determine the protein levels of PTEN, Akt, p-Akt, caspase-3, caspase-9, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). The results showed that HepG2 cells were the best cell line for subsequent experiments. The dual luciferase reporter assay confirmed that miR-1297 could bind to the 3'-untranslated region(3'UTR) in the mRNA of PTEN. The medicated plasma inhibited the proliferation of HepG2 cells, and the optimal intervention concentration and time were 20% and 72 h. Compared with the blank plasma, the Bupleuri Radix-Paeoniae Radix Alba medicated plasma, miR-1297 inhibitor, miR-1297 inhibitor + medicated plasma all inhibited the proliferation, invasion, and migration of HepG2 cells, increased the proportion of cells in the G_0/G_1 phase, decreased the proportion of cells in the S phase, and increased the apoptosis rate. The medicated plasma down-regulated the mRNA levels of miR-1297, PI3K, and Akt and up-regulated the mRNA level of PTEN. In addition, it up-regulated the protein levels of PTEN, Bax, caspase-3, and caspsae-9 and down-regulated the protein levels of p-Akt, p-PI3K, and Bcl-2. In conclusion, Bupleuri Radix-Paeoniae Radix Alba medicated plasma can inhibit the expression of miR-1297 in HepG2 hepatoma cells, promote the expression of PTEN, and negatively regulate PI3K/Akt signaling pathway, thereby inhibiting the proliferation and inducing the apoptosis of HepG2 cells.

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.

Pyridoxine challenge reflects pediatric hypophosphatasia severity and thereby examines tissue-nonspecific alkaline phosphatase's role in vitamin B6 metabolism.

Alkaline phosphatase (ALP) is detected in most human tissues. However, ALP activity is routinely assayed using high concentrations of artificial colorimetric substrates in phosphate-free laboratory buffers at lethal pH. Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of the ALPL gene that encodes the ALP isoenzyme expressed in bone, liver, kidney, and elsewhere and is therefore designated "tissue-nonspecific" ALP (TNSALP). Consequently, HPP harbors clues concerning the biological function of this phosphohydrolase that is anchored onto the surface of cells. The biochemical signature of HPP features low serum ALP activity (hypophosphatasemia) together with elevated plasma levels of three natural substrates of TNSALP: i) phosphoethanolamine (PEA), a component of the linkage apparatus that binds ALPs and other proteins to the plasma membrane surface; ii) inorganic pyrophosphate (PPi), an inhibitor of bone and tooth mineralization; and iii) pyridoxal 5'-phosphate (PLP), the principal circulating vitameric form of vitamin B6 (B6). Autosomal dominant and autosomal recessive inheritance involving several hundred ALPL mutations underlies the remarkably broad-ranging expressivity of HPP featuring tooth loss often with muscle weakness and rickets or osteomalacia. Thus, HPP associates the "bone" isoform of TNSALP with biomineralization, whereas the physiological role of the "liver", "kidney", and other isoforms of TNSALP remains uncertain. Herein, to examine HPP's broad-ranging severity and the function of TNSALP, we administered an oral challenge of pyridoxine (PN) hydrochloride to 116 children with HPP. We assayed both pre- and post-challenge serum ALP activity and plasma levels of PLP, the B6 degradation product pyridoxic acid (PA), and the B6 vitamer pyridoxal (PL) that can enter cells. Responses were validated by PN challenge of 14 healthy adults and 19 children with metabolic bone diseases other than HPP. HPP severity was assessed using our HPP clinical nosology and patient height Z-scores. PN challenge of all study groups did not alter serum ALP activity in our clinical laboratory. In HPP, both the post-challenge PLP level and the PLP increment correlated (Ps < 0.0001) with the clinical nosology and height Z-scores (Rs = +0.6009 and + 0.4886, and Rs = -0.4846 and - 0.5002, respectively). In contrast, the plasma levels and increments of PA and PL from the PN challenge became less pronounced with HPP severity. We discuss how our findings suggest extraskeletal TNSALP primarily conditioned the PN challenge responses, and explain why they caution against overzealous B6 supplementation of HPP.

A study of the biological effects of low-level light.

Low-level light therapy (LLLT), also known as photo biomodulation (PBM), is a type of optical therapy that uses red or near-infrared lasers or light-emitting diodes (LEDs) for medical treatment. The laser wavelengths involved in PBM typically range between 600-700 nm and 780-1100 nm, with power densities ranging between 5 mW/cm2 and 5 W/cm2. PBM is a series of biochemical cascades exhibited by biological tissues after absorbing a certain amount of energy from light. PBM has been widely used in clinical practice in the past 20 years, and numerous clinical trials have demonstrated its biological efficacy. However, the underlying mechanisms have not yet been fully explored. In this paper, we have summarized the research into PBM over the past two decades, to identify the important mechanisms of the biological effects of PBM from the perspective of molecular mechanisms, cellular levels, and tissue changes. We hope our study provide a theoretical basis for future investigations into the underlying mechanisms.

Therapeutic effects of acupuncture therapy for kidney function and common symptoms in patients with chronic kidney disease: a systematic review and meta-analysis.

Purpose: The number of clinical reports of acupuncture therapy in chronic kidney disease (CKD) is gradually increasing. This systematic review and meta-analysis aim to examine the therapeutic role of acupuncture therapy in kidney function and common symptoms in CKD patients.Methods: We searched Embase, PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, WanFang, and WeiPu for randomized controlled trials comparing acupuncture treatment with control or placebo groups. We assessed the effect of acupuncture therapy in CKD patients using a meta-analysis with the hartung-knapp-sidik-jonkman random effects model. In addition, we visualized keyword co-occurrence overlay visualization with the help of VOSviewer software to describe the research hotspots of acupuncture therapy and CKD.Results: A total of 24 studies involving 1494 participants were included. Compared to the control group, acupuncture therapy reduced serum creatinine levels (standardized mean difference [SMD]: -0.57; 95% CI -1.05 to -0.09) and relieved pruritus (SMD: -2.20; 95% CI -3.84, -0.57) in patients with CKD, while the TSA showed that the included sample size did not exceed the required information size. The included studies did not report acupuncture-related adverse events.Conclusions: Acupuncture is an effective and safe treatment for improving kidney function and relieving pruritic symptoms in patients with CKD, but the very low evidence may limit this conclusion. The TSA suggests that high-quality trials are needed to validate the efficacy of acupuncture therapy.

Acupuncture therapy may improve kidney function and relieve pruritus symptoms in CKD patients, but both are very low evidence.Trial sequential analysis shows insufficient evidence for acupuncture therapy in CKD patients.Future research could focus on the role of acupuncture for functional capacity, insomnia, and pain in CKD patients.

Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment.

OBJECTIVE: This study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC). METHODS: Traditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice. RESULTS: The major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8+ and IFN-γ+/CD4+ T cell levels while decreasing the PD-1+/CD8+ T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-γ, and TNF-α levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated. CONCLUSION: BP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.

Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis.

Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.

Risk factors for arteriovenous fistula dysfunction in hemodialysis patients: a retrospective study.

Arteriovenous fistula (AVF) is the first choice of vascular access in hemodialysis (HD) patients. However, the correlations between patient factors and the arteriovenous fistula patency remain unclear. Therefore, our study investigates the risk factors associated with AVF dysfunction in HD patients. A total of 233 end-stage renal disease (ESDR) patients who met the study inclusion criteria in the Nephrology Department of Hunan Provincial People's Hospital between December 2020 and June 2022 were included in this study. The baseline demographic, clinical and laboratory parameters were collected at the time of AVF creation and analyzed. Of the 233 ESRD patients, 146 (62.7%) were male and the mean age was 56.11 ± 12.14 (21-82) years. The patients were followed for a median time of 14 months. Kaplan-Meier analysis showed a 6-, 12- and 24-month post-placement survival of 87.1%, 82.8% and 80.7%, respectively. Univariate Cox regression analysis revealed weight (HR, 1.03; P = 0.03) as a predictor for the loss of vascular access functionality. In addition, multivariate Cox regression analysis further demonstrated that sex (HR, 3.41; P = 0.03), weight (HR 1.08; P < 0.01) and phosphorus level (HR: 3.03; P = 0.01) are independent risk factors for AVF dysfunction. AVF dysfunction is highly associated with several risk factors including weight, phosphorus level, and sex. Positive intervention strategies targeting these potential factors, such as weight loss or oral phosphate binders could improve the long-term success of AVF.

The curative effect of fire needling combined with filiform needling on tension-type headache and its effect on the tenderness of pericranial muscles. / ç«é’ˆè”åˆæ¯«é’ˆæ²»ç–—ç´§å¼ æ€§å¤´ç—›çš„ç–—æ•ˆåŠå¯¹é¢ å‘¨è‚Œè‚‰åŽ‹ç—›çš„å½±å“.

OBJECTIVES: To observe the curative effect of fire needling pricking pericranial tender points combined with filiform needling on tension-type headache (TTH) and its effect on pericranial muscle tenderness, and explore the correlation between changes of headache symptoms and pericranial muscle tenderness in TTH, to analyze the influence of pericranial muscle tenderness on TTH. METHODS: A total of 41 TTH patients in the treatment group and 38 TTH patients in the control group completed the study. The patients in the treatment group were treated with fire needling at pericranial tender points combined with filiform needling at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Touwei (ST8) and Fengchi (GB20). The patients in the control group were only treated with the same filiform needling as the treatment group. Patients in the two groups were treated twice a week for 8 weeks. Before and after treatment, the days of headache onset, the number and distribution of pericranial muscle tender points were recorded, the degree of headache was evaluated by visual analogue scale and the threshold of pericranial muscle tender points were measured. The correlations between the changes of the days and degree of headache onset and the changes of the number and threshold of pericranial muscle tender points were analyzed. The effective rates in the two groups were calculated. RESULTS: Compared with those before treatment, the days of headache onset and the degree of headache were decreased (P<0.05) in the two groups；the number of pericranial muscle tender points was decreased (P<0.05) and the tenderness threshold was increased (P<0.05) in the treatment group. After treatment, compared with the control group, the days of headache onset, the degree of headache, and the number of pericranial muscle tender points were decreased (P<0.05), and the tenderness threshold was increased (P<0.05) in the treatment group. The decrease of the days and degree of headache was positively correlated with the decrease of number and the increase of tenderness threshold of pericranial muscle tender points (P<0.05). The effective rate in the treatment group was 87.80% (36/41), which was higher than 57.89% (22/38) in the control group (P<0.05). The most common anatomic location of tender points in baseline was superior trapezius muscle, followed by sternocleidomastoid muscle, superior nuchal line, temporal muscle, masseter muscle, etc. CONCLUSIONS: The fire needling at the pericranial muscle tender points combined with filiform needling on TTH patients can significantly improve the clinical symptoms and reduce the pericranial muscle tenderness. The pericranial muscle tenderness is an important factor in the pathogenesis of TTH.

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.

A chromosome-level genome assembly of the Knoxia roxburghii (Rubiaceae).

Knoxia roxburghii is a well-known medicinal plant that is widely distributed in southern China and Southeast Asia. Its dried roots, known as hongdaji in traditional Chinese medicine, are used to treat a range of diseases, including cancers, carbuncles, and ascites. In this study, we report a de novo chromosome-level genome sequence for this diploid plant, which has a length of approximately 446.30 Mb with a contig N50 size of 42.26 Mb and scaffold N50 size of 44.38 Mb. Approximately 99.78% of the assembled sequences were anchored to 10 pseudochromosomes and 3 gapless assembled chromosomes were included in this assembly. A total of 24,507 genes were annotated, along with 68.92% of repetitive elements. Overall, our results will facilitate further active component biosynthesis for K. roxburghii and provide insights for future functional genomic studies and DNA-informed breeding.

Correlating chemistry and mass transport in sustainable iron production.

Steelmaking contributes 8% to the total CO2 emissions globally, primarily due to coal-based iron ore reduction. Clean hydrogen-based ironmaking has variable performance because the dominant gas-solid reduction mechanism is set by the defects and pores inside the mm- to nm-sized oxide particles that change significantly as the reaction progresses. While these governing dynamics are essential to establish continuous flow of iron and its ores through reactors, the direct link between agglomeration and chemistry is still contested due to missing measurements. In this work, we directly measure the connection between chemistry and agglomeration in the smallest iron oxides relevant to magnetite ores. Using synthesized spherical 10-nm magnetite particles reacting in H2, we resolve the formation and consumption of wüstite (Fe1-xO)-the step most commonly attributed to whiskering. Using X-ray diffraction, we resolve crystallographic anisotropy in the rate of the initial reaction. Complementary imaging demonstrated how the particles self-assemble, subsequently react, and grow into elongated "whisker" structures. Our insights into how morphologically uniform iron oxide particles react and agglomerate in H2 reduction enable future size-dependent models to effectively describe the multiscale aspects of iron ore reduction.

Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels.

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of 'state-target identification and treatment': a scooping review.

Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour's microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation-an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour's inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1ß), transforming growth factor-beta (TGF-ß), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin's novel model of "state-target differentiation" and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy-a harmonious integration of state identification, target recognition, and simultaneous regulation-aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data.

INTRODUCTION: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. METHODS: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999-2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5-6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711-0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399-0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659-0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675-0.888, P < 0.001). CONCLUSION: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Preparation of Ribes nigrum L. polysaccharides-stabilized selenium nanoparticles for enhancement of the anti-glycation and α-glucosidase inhibitory activities.

Seven kinds of selenium nanoparticles (RP-SeNPs) were prepared by using the polysaccharides extracted from Ribes nigrum L. (RP) as the stabilizer and dispersant. Among them, RP-SeNPs-1 (94.2 nm), RP-SeNPs-2 (101.2 nm) and RP-SeNPs-3 (107.6 nm) with relatively smaller mean particle size exhibited stronger α-glucosidase inhibitory activity than other RP-SeNPs (115.3-164.2 nm) and SeNPs (288.9 nm). Ultraviolet-visible spectrophotometry, Fourier transform-infrared, X-ray diffraction, energy dispersive X-ray and X-ray photoelectron spectroscopy analyses confirmed that SeNPs were ligated with RP to form nanocomposites and displayed amorphous form. Electron microscopy images revealed that RP-SeNPs-1 - RP-SeNPs-3 were regular shape spherical nanocomposites with much better dispersion than SeNPs. Compared with SeNPs, RP-SeNPs displayed relatively high thermal, storage, pH and salt ion stability. Moreover, RP-SeNPs-1-RP-SeNPs-3 showed significantly better anti-glycation and α-glucosidase inhibitory activity than SeNPs, especially RP-SeNPs-1 with the smallest particle size. Inhibitory kinetics analysis indicated that SeNPs and RP-SeNPs inhibited α-glucosidase with competitive type and reversible mechanism. In addition, the conformation of the α-glucosidase was changed after binding with the SeNPs and RP-SeNPs-1. Fluorescence quenching and isothermal titration calorimetry assays revealed that these two nanoparticles could interact with α-glucosidase to form non-fluorescent complexes through hydrogen bonding, and the formation was spontaneously driven by enthalpy.

Electroacupuncture attenuates myocardial ischemia-reperfusion injury by inhibiting microglial engulfment of dendritic spines.

A major side effect of reperfusion therapy following myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture preconditioning (EA-pre) has a long history in the treatment of cardiovascular diseases. Here, we demonstrate how EA-pre attenuates MIRI by affecting the phagocytosis of neuronal dendritic spines of microglia of the fastigial nucleus (FNmicroglia). We observed that EA-pre increased activity in FNGABA and then improved myocardial injury by inhibiting abnormal activities of glutaminergic neurons of the FN (FNGlu) during MIRI. Interestingly, we observed changes in the quantity and shape of FN microglia in mice treated with EA-pre and a decrease in the phagocytosis of FNGABA neuronal dendritic spines by microglia. Furthermore, the effects of improving MIRI were reversed when EA-pre mice were chemically activated by intra-FN lipopolysaccharide injection. Overall, our results provide new insight indicating that EA-pre regulates microglial engulfment capacity, thus promoting the improvement of cardiac sympathetic nervous disorder during MIRI.

Could long-term dialysis vintage and abnormal calcium, phosphorus and iPTH control accelerate aging among the maintenance hemodialysis population?

OBJECTIVE: Aging is a complex process of physiological dysregulation of the body system and is common in hemodialysis patients. However, limited studies have investigated the links between dialysis vintage, calcium, phosphorus, and iPTH control and aging. The purpose of the current study was to examine these associations. METHODS: During 2020, a cross-sectional study was conducted in 3025 hemodialysis patients from 27 centers in Anhui Province, China. Biological age was calculated by a formula using chronological age and clinical indicators. The absence of the target range for serum phosphorus (0.87-1.45 mmol/L), corrected calcium (2.1-2.5 mmol/L) and iPTH (130-585 pg/mL) were identified as abnormal calcium, phosphorus, and iPTH control. RESULTS: A total of 1131 hemodialysis patients were included, 59.2% of whom were males (669/1131). The mean (standard deviation) of actual age and biological age were 56.07 (12.79) years and 66.94 (25.88), respectively. The median of dialysis vintage was 4.3 years. After adjusting for the confounders, linear regression models showed patients with abnormal calcium, phosphorus, and iPTH control and on hemodialysis for less than 4.3 years (B = 0.211, p = .002) or on hemodialysis for 4.3 years or more (B = 0.302, p < .001), patients with normal calcium, phosphorus, and iPTH control and on hemodialysis for 4.3 years or more (B = 0.087, p = .013) had a higher biological age. CONCLUSION: Our findings support the hypothesis that long-term hemodialysis and abnormal calcium, phosphorus, and iPTH control may accelerate aging in the hemodialysis population. Further studies are warrant to verify the significance of maintaining normal calcium-phosphorus metabolism in aging.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

BACKGROUND: The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. PURPOSE: This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. METHODS: We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. RESULTS: According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. CONCLUSIONS: This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.