FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability. Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. Through screening and structural optimization, the optimal lead compound PROTAC Z29 showed better specificity than Gilteritinib. Z29 induced FLT3 degradation through the proteasome pathway and inhibited tumor growth in subcutaneous xenograft mice. We verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model compared to Gilteritinib. The combination of Z29 and Venetoclax showed better anti-tumor effects, lower platelet toxicity, and lower hepatic toxicity in FLT3-ITD+ models. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.

DCPIB attenuates ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.

The inflammatory response plays an indispensable role in ischemia-reperfusion injury, the most significant of which is the inflammatory response caused by microglial polarization. Anti-inflammatory therapy is also an important remedial measure after failed vascular reconstruction. Maintaining the internal homeostasis of the brain is a crucial measure for suppressing the inflammatory response. The mechanism underlying the relationship between DCPIB, a selective blocker of volume-regulated anion channels (VRAC), and inflammation induced by cerebral ischemia-reperfusion injury is currently unclear. The purpose of this study was to investigate the relationship between DCPIB and microglial M1/M2 polarization-mediated inflammation after cerebral ischemia-reperfusion injury. C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). DCPIB was administered by a lateral ventricular injection within 5 min after reperfusion. Behavioral assessments were conducted at 1, 3, and 7 days after tMCAO/R. Pathological injuries were evaluated using TTC assay, HE and Nissl staining, brain water content measurement, and immunofluorescence staining. The levels of inflammatory cytokines were analyzed using qPCR and ELISA. Additionally, the phenotypic variations of microglia were examined using immunofluorescence staining. In mouse tMCAO/R model, DCPIB administration markably reduced mortality, improved behavioral performance, and alleviated pathological injury. DCPIB treatment significantly inhibited the inflammatory response, promoted the conversion of M1 microglia to M2 microglia via the MAPK signaling pathway, and ultimately protected neurons from the microglia-mediated inflammatory response. In addition, DCPIB inhibited oxidative stress induced by cerebral ischemia-reperfusion injury. In conclusion, DCPIB attenuates cerebral ischemia-reperfusion injury by regulating microglial M1/M2 polarization and oxidative stress.

Exploration of shared gene signatures and molecular mechanisms between type 2 diabetes and osteoporosis.

Type 2 diabetes mellitus (T2D) and osteoporosis (OP) are systemic metabolic diseases and often coexist. The mechanism underlying this interrelationship remains unclear. We downloaded microarray data for T2D and OP from the Gene Expression Omnibus (GEO) database. Using weighted gene co-expression network analysis (WGCNA), we identified co-expression modules linked to both T2D and OP. To further investigate the functional implications of these associated genes, we evaluated enrichment using ClueGO software. Additionally, we performed a biological process analysis of the genes unique in T2D and OP. We constructed a comprehensive miRNA-mRNA network by incorporating target genes and overlapping genes from the shared pool. Through the implementation of WGCNA, we successfully identified four modules that propose a plausible model that elucidates the disease pathway based on the associated and distinct gene profiles of T2D and OP. The miRNA-mRNA network analysis revealed co-expression of PDIA6 and SLC16A1; their expression was upregulated in patients with T2D and islet ß-cell lines. Remarkably, PDIA6 and SLC16A1 were observed to inhibit the proliferation of pancreatic ß cells and promote apoptosis in vitro, while downregulation of PDIA6 and SLC16A1 expression led to enhanced insulin secretion. This is the first study to reveal the significant roles of PDIA6 and SLC16A1 in the pathogenesis of T2D and OP, thereby identifying additional genes that hold potential as indicators or targets for therapy.

Enhancing the nonlinear rheological property and digestibility of mung bean flour gels using controlled microwave treatments: Effect of starch debranching and protein denaturation.

In this study, we examined the possibility of using industrial microwave processing to enhance the gelling properties and reduce the starch digestibility of mung bean flour (MBF). MBF (12.6 % moisture) was microwaved at a power of 6 W/g to different final temperatures (100-130 °C), and then its structural and functional properties were characterized. The microwave treatment had little impact on the crystalline structure or amylose content of the starch, but it roughened the starch granule surfaces and decreased the short-range ordered structure and degree of branching. In addition, the extent of mung bean protein denaturation caused by the microwave treatment depended on the final temperature. Slightly denaturing the proteins (100 °C) did not affect the nature of the gels (protein phase dispersed in a starch phase) but the gel network became more compact. Moderately denaturing the proteins (110-120 °C) led to more compact and homogeneous starch-protein double network gels. Excessive protein denaturation (130 °C) caused the gel structure to become more heterogeneous. As a result, the facilitated tangles between starch chains by more linear starch molecules after debranching, and the protein network produced by moderate protein denaturation led to the formation of stronger gel and the improvement of plasticity during large deformation (large amplitude oscillatory shear-LAOS). Starch recrystallization, lipid complexion, and protein network retard starch digestion in the MBF gels. In conclusion, an industrial microwave treatment improved the gelling and digestive properties of MBF, and Lissajous curve has good adaptability in characterizing the viscoelasticity of gels under large deformations.

Creep-type all-solid-state cathode achieving long life.

Electrochemical-mechanical coupling poses enormous challenges to the interfacial and structural stability but create new opportunities to design innovative all-solid-state batteries from scratch. Relying on the solid-solid constraint in the space-limited domain structure, we propose to exploit the lithiation-induced stress to drive the active materials creep, thereby improving the structural integrity. For demonstration, we fabricate the creep-type all-solid-state cathode using creepable Se material and an all-in-one rigid ionic/electronic conducting Mo6Se8 framework. As indicated by the in-situ experiment and numerical simulation, this cathode presents unique capabilities in improving interparticle contact and avoiding particle fracture, leading to its superior electrochemical performance, including a superior long-cycle life of more than 3000 cycles at 0.5 C and a high volumetric energy density of 2460 Wh/L at the cathode level. We believe this innovative strategy to utilize mechanics to boost the electrochemical performance could shed light on the future design of all-solid-state batteries for practical applications.

Association of GLP-1 receptor agonists and hepatocellular carcinoma incidence and hepatic decompensation in patients with type 2 diabetes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70 percent of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), FDA-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio (HR) and 95% confidence interval (CI) calculated. RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with HR of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with six other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared to other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Three-year follow-up of a novel orthopedic ward fracture liaison services (OWFLS) model.

OBJECTIVE: We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. METHODS: This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020. We compared rates of bone metabolic index testing, treatment, and adherence; symptomatic improvement; and recurrent fracture between groups. RESULTS: Rates of bone metabolism index testing (50% vs. 0%) and medication use (94.2% vs. 64.2%) were significantly higher after OWFLS implementation. There was no significant difference in adherence rates at 3 months between groups (97.3% vs. 93.5%). Adherence rates at 1 and 3 years were better in group B than A (73.5% vs. 51.9%; 57.5% vs. 26%, respectively). Recurrence of bone pain at 1 and 3 years was significantly lower in group B than A (20.4% vs. 46.8%; 45.1% vs. 76.6%, respectively). CONCLUSIONS: OWFLS improved the detection rate of bone metabolism indicators, treatment rate, and patient adherence and reduced recurrence of bone pain. OWFLS may be suitable for settings lacking human resources.

Co-delivery of fucoxanthin and Twist siRNA using hydroxyethyl starch-cholesterol self-assembled polymer nanoparticles for triple-negative breast cancer synergistic therapy.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.

Sparse-view CT reconstruction based on group-based sparse representation using weighted guided image filtering.

OBJECTIVES: In the past, guided image filtering (GIF)-based methods often utilized total variation (TV)-based methods to reconstruct guidance images. And they failed to reconstruct the intricate details of complex clinical images accurately. To address these problems, we propose a new sparse-view CT reconstruction method based on group-based sparse representation using weighted guided image filtering. METHODS: In each iteration of the proposed algorithm, the result constrained by the group-based sparse representation (GSR) is used as the guidance image. Then, the weighted guided image filtering (WGIF) was used to transfer the important features from the guidance image to the reconstruction of the SART method. RESULTS: Three representative slices were tested under 64 projection views, and the proposed method yielded the best visual effect. For the shoulder case, the PSNR can achieve 48.82, which is far superior to other methods. CONCLUSIONS: The experimental results demonstrate that our method is more effective in preserving structures, suppressing noise, and reducing artifacts compared to other methods.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosis.

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.

Comparison of short-term clinical outcomes of a diffractive trifocal intraocular lens with phacoemulsification and femtosecond laser assisted cataract surgery.

PURPOSE: To evaluate short-term visual and refractive outcomes after implantation of a diffractive trifocal intraocular lens (IOL) in cataract patients with phacoemulsification (PHACO) and femtosecond laser assisted cataract surgery (FLACS). SETTING: Department of Ophthalmology, Shanghai Aier Eye Hospital, China. DESIGN: A retrospective, observational study. METHODS: Patients who underwent cataract surgery combined with Acrysoft IQ PanOptix trifocal IOL implantation were enrolled and divided into three groups: PHACO group, LAstig-FLACS group (astigmatism less then 1D) and HAstig-FLACS group (astigmatism more than 1D). Logarithm of the minimum angle of resolution (logMAR) visual acuity of uncorrected distance (UDVA), intermediate (UIVA), near visual (UNVA), defocus curve, surgically induced astigmatism (SIA) were evaluated in 1 months postoperatively and wavefront aberrations were evaluated in 6 months. RESULTS: 101 eyes of 60 patients were included with 31 eyes in PHACO group, 45 eyes in LAstig-FLACS group and 25 eyes in HAstig-FLACS group. Significant difference was found of internal Strehl Ratio (SR) between PHACO and LAstig-FLACS group (P = 0.026). In PHACO group, 79.31%, 86.21%, 72.41% of eyes gain visual acuity LogMAR 0.1 or more in UDVA, UIVA and UNVA, while 83.72%, 93.02%, 93.02% of those in LAstig-FLACS group and 92.00%, 84.00%, 76.00% in HAstig-FLACS group. CONCLUSIONS: Panoptix diffractive trifocal IOL provides satisfied visual outcome in no matter FLACS or PHACO. Besides, trifocal IOL implantation via FLACS can provide a better accumulative visual acuity outcome at all distance than PHACO in 1 month. Femtosecond laser assisted limbal relaxing incisions (FLLRIs) is an excellent way to reduce a patient's corneal astigmatism.

Polarization-resolved super-resolution second-harmonic generation imaging based on multifocal structured illumination microscopy.

Polarization-resolved second-harmonic generation (PSHG) microscopy is widely used in investigating the structural and morphological alterations of collagen. However, the resolution of second-harmonic generation (SHG) imaging remains constrained by optical diffraction, resulting in the polarization extraction of collagen characteristics from the average properties of collagen fibers. In this study, multifocal structured illumination microscopy (MSIM) was combined with PSHG to achieve polarization-resolved super-resolution imaging of second-harmonic generation signals. For the first time to our knowledge, periodic structures with an average pitch of 277 nm were observed in mouse tail tendons using optical microscopy, and the orientation angle of fibrils within each period was found to exhibit an alternating arrangement along the axis in a regular pattern.

p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6.

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-ß-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.

Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double-blind, controlled trial.

BACKGROUND: To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory study aimed to assess the efficacy and safety of remimazolam at a single induced dose for deep sedation in elderly patients undergoing diagnostic flexible bronchoscopy (DFB), and compare with midazolam, a commonly used sedative. METHODS: A total of 100 elderly patients (age range 65-80 yr; American Society of Anesthesiologists Physical Status I-III) undergoing DFB were randomly allocated into 2 groups according to the sedatives used for induction: the remimazolam group and the midazolam group. Sedation induction was initiated by an intravenous bolus of remimazolam (0.135 mg/kg) or midazolam (0.045 mg/kg), respectively, both groups were combined with a high-dose of alfentanil (18 µg/kg), and supplemented with high-flow nasal cannula (HFNC) oxygen supply at a flow rate of 45 L/min. If the target depth of sedation was not achieved, propofol would be titrated as a rescue. The primary outcome was the success rate of sedation at a single induced dose to achieve target depth (Ramsay sedation score [RSS] = 4) during induction, intraoperative changes in vital signs, postoperative follow-up situation and incidence of post-bronchoscopy adverse events were evaluated as secondary outcomes. RESULTS: The success rate of sedation in the remimazolam group was significantly higher than that in the midazolam group (65.2% vs 39.6%, P = .013), while the incidence of extra sleep within 6 hours after procedure was lower in the remimazolam group as compared to the midazolam group (10.9% vs 31.3%, P = .016). No statistically significant differences were observed between the 2 groups regarding hemodynamic fluctuations, incidence of hypoxemia, and cough response during the procedure, as well as postoperative recall, willingness to undergo reexamination, and other post-bronchoscopy adverse events. CONCLUSIONS: Bolus administration of remimazolam offers advantages over midazolam for deep sedation in elderly patients undergoing DFB, in terms of a higher success rate of sedation and a lower incidence of extra sleep within 6 hours after procedure, though the safety profiles of both groups were favorable.

Bidirectional crosstalk between the epithelial-mesenchymal transition and immunotherapy: A bibliometric study.

Immunotherapy has recently attracted considerable attention. However, currently, a thorough analysis of the trends associated with the epithelial-mesenchymal transition (EMT) and immunotherapy is lacking. In this study, we used bibliometric tools to provide a comprehensive overview of the progress in EMT-immunotherapy research. A total of 1,302 articles related to EMT and immunotherapy were retrieved from the Web of Science Core Collection (WOSCC). The analysis indicated that in terms of the volume of research, China was the most productive country (49.07%, 639), followed by the United States (16.89%, 220) and Italy (3.6%, 47). The United States was the most influential country according to the frequency of citations and citation burstiness. The results also suggested that Frontiers in Immunotherapy can be considered as the most influential journal with respect to the number of articles and impact factors. "Immune infiltration," "bioinformatics analysis," "traditional Chinese medicine," "gene signature," and "ferroptosis" were found to be emerging keywords in EMT-immunotherapy research. These findings point to potential new directions that can deepen our understanding of the mechanisms underlying the combined effects of immunotherapy and EMT and help develop strategies for improving immunotherapy.

Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

Single-pool model urea clearance index is associated with sarcopenia and nutritional status in patients undergoing maintenance hemodialysis: a cross-sectional study.

BACKGROUND: The single-pool model urea clearance index (single-pool Kt/Vurea; spKt/V) is the most commonly used method for dialysis adequacy assessment. However, only a few studies have examined the relationship between spKt/V values and parameters related to sarcopenia and nutritional status. This study aimed to evaluate whether the spKt/V is an indicator of sarcopenia and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: A total of 142 patients were included in this single-center, cross-sectional study. Venous blood samples were collected shortly before the hemodialysis session. The adequacy of dialysis in patients receiving MHD was assessed using spKt/V. Sarcopenia was identified according to the Asian Working Group for Sarcopenia (2019) definition. Receiver operating characteristic curve and area under the curve were used to evaluate the predictive value of spKt/V in sarcopenia. Univariate and multivariate binary logistic regression analyses were used to determine the association between spKt/V and sarcopenia and nutritional status. RESULTS: The mean spKt/V level was 1.3 ± 0.2, the prevalence of sarcopenia was 15.5% in patients on MHD. The best cutoff value of spKt/V in sarcopenia was 1.45 for both sexes, 1.33 and 1.45 for men and women, respectively (P < 0.05). The multivariate binary logistic regression shown that the spKt/V was independently positively associated with sarcopenia (OR = 122.88, 95% CI = 0.64-0.87, P = 0.002). Grouping spKt/V by the best cutoff value, when spKt/V ≥ 1.45, the OR of sarcopenia was 11.75 (95% CI = 3.16-43.67, P < 0.001). Subgroup analyses showed that when spKt/V ≥ 1.33 in men and spKt/V ≥ 1.45 in woman, the OR of sarcopenia was 9.73 (95% CI = 2.25-42.11, P = 0.002) and 14.52 (95% CI = 1.06-199.67, P = 0.045), respectively. CONCLUSIONS: The present study showed that spKt/V was an important influencing factor of sarcopenia and malnutrition in Asian patients on MHD.