Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

Objective To study the traditional Chinese medicine(TCM)constitution characteristics of overweight/obese patients in Shanghai region and to investigate the correlation of TCM constitution with body composition.Methods Relevant data were collected from the patients with complete information of TCM constitution and human body composition analysis who visited the specialized outpatient clinic of acup-moxibustion catgut embedding therapy in the Department of Endocrinology,Shanghai Tenth People's Hospital from August 2020 to December 2022.The patients were divided into a normal body mass group(BMI＜24 kg/m2),an overweight group(24 kg/m2≤BMI＜28 kg/m2)and obesity group(BMI≥28 kg/m2),and then the distribution of TCM constitution types in the three groups of patients were analyzed.After that,the correlation between TCM constitution and body composition were explored with multiple regression analysis.Results(1)A total of 315 patients were included,of which 43 patients had normal body mass,85 patients were overweight and 187 patients were obese.(2)The TCM constitution types in descending order of the composition ratio in the normal body mass group and in the overweight group were spleen deficiency constitution,liver stagnation constitution,damp-heat constitution,yang deficiency constitution,and yin deficiency constitution,in the obese group were spleen deficiency constitution,yang deficiency constitution,damp-heat constitution,liver stagnation constitution,and yin deficiency constitution,and in the overweight/obese group were spleen deficiency constitution,damp-heat constitution,yang deficiency constitution,liver stagnation constitution,and yin deficiency constitution.No statistically significant differences of the distribution of TCM constitution types were shown between normal body bass population and overweight/obese population(P＞0.05).In both normal body mass population and overweight/obese population,the single body constitution type was common,and biased constitution was rare,and there was no statistically significant difference when comparing between the two groups(P＞0.05).(3)The results of multiple regression analysis showed that the basal metabolism of all patients was positively correlated with yang deficiency constitution and was negatively correlated with damp-heat constitution,and the differences were statistically significant(P＜0.01).It is indicated that if the score of yang deficiency constitution rose by one point,the basal metabolism would increase by 0.54 kcal,and if the score of damp-heat constitution decreased by one point,the basal metabolism would decrease by 1.005 kcal.Conclusion In Shanghai region,obesity may be the main indication of the variation of the body constitution.In addition to spleen deficiency constitution,the proportions of yang deficiency constitution,damp-heat constitution and liver stagnation constitution are also higher in obese patients.In terms of the correlation between TCM constitution and body composition,basal metabolism is positively correlated with yang deficiency constitution and is negatively correlated with damp-heat constitution.Therefore,for the patients with yang deficiency constitution and damp-heat constitution,the influence of the basal metabolism level on the development of the disease should be taken into account.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective To observe the clinical efficacy of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels for the treatment of acute pancreatitis of pathogenic-cold accumulation and retention type.Methods A total of 78 patients with acute pancreatitis of pathogenic-cold accumulation and retention type were randomly divided into a study group and a control group,39 cases in each group.The control group was treated with conventional western medicine,and the study group was treated with oral use or nasogastric feeding of Dahuang Fuzi Decoction on the basis of treatment for the control group.The course of treatment covered seven days.The two groups were observed in the changes of serum pancreatic enzyme indicators of serum amylase and lipase,inflammatory factors of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6)and interleukin-8(IL-8),acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,and modified CT severity index(MCTSI)score before and after treatment.The time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation were compared between the two groups.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,there was one patient falling off separately from the study group and the control group,and 38 patients in each group were eventually included in the efficacy statistics.(2)After seven days of treatment,the total effective rate of the study group was 86.84％(33/38),and that of the control group was 78.95％(30/38).The intergroup comparison(tested by rank sum test)showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the serum levels of pancreatic enzyme indicators of amylase and lipase in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum amylase and lipase levels in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the serum levels of inflammatory factors of CRP,PCT,IL-6 and IL-8 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum CRP,PCT,IL-6 and IL-8 levels in the study group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the APACHE Ⅱ and MCTSI scores of the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of APACHE Ⅱ and MCTSI scores in the study group was significantly superior to that in the control group(P＜0.05).(6)For the time of symptom relief,the time for abdominal pain relief,time for abdominal distension relief,and time for anal defecation in the study group were significantly shortened compared with those in the control group,and the differences were statistically significant(P＜0.05).(7)No obvious adverse reactions occurred in the two groups during the treatment,indicating high safety.Conclusion On the basis of conventional treatment,the use of modified Dahuang Fuzi Decoction following the therapy of unblocking bowels exerts certain efficacy for the treatment of patients with acute pancreatitis of pathogenic-cold accumulation and retention type.The therapy is effective on relieving the symptoms and signs of patients,and decreasing the level of serum pancreatic enzyme indicators and inflammatory factors.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Aim To evaluate the effect of hyperoside/chitosan-nanoparticles(Hyp-NPs)on bone marrow mesenchymal stem cells(BMSCs)in vitro cell experi-ments and the underlying mechanism,and to conduct in vivo animal experiments to investigate the synergistic effect of Hyp-NPs and BMSCs on repairing endometrial damage in rats.Methods BMSCs were identified by flow cytometry.Hyp-NPs were prepared by ion crosslinking method,characterized and evaluated by laser particle size analyzer and transmission electron microscopy.The effects of different concentrations of Hyp-NPs on the migration of BMSCs were evaluated by scratch assay and immunofluorescence.NRF2 lentivir-us vector was constructed to explore the mechanism of Hyp-NPs on BMSCs.In animal experiments,Hyp-NPs loaded with BMSCs were co-transplanted into the uter-ine cavity of a rat model of endometrial injury.HE,Masson,IHC,TUNEL,and ELISA experiments were used to systematically evaluate the repair effect and pregnancy function of the composite formulation on rat endometrial injury from multiple aspects and angles,including general pathology,fibrosis,receptivity,cell proliferation,angiogenesis,stem cell recruitment,and inflammation of the endometrium.Results BMSCs were successfully isolated and cultured.Hyp-NPs with high stability and small particle size were successfully prepared.Scratch experiments indicated that Hyp-NPs could promote the migration of BMSCs.By successfully constructing a lentiviral NRF2 vector and oxidative damage model for BMSCs,immunofluorescence experi-ments showed that Hyp-NPs could regulate the biologi-cal axis of BMSCs by activating NRF2.Animal experi-ments showed that the synergistic administration of Hyp-NPs and BMSCs could increase endometrial thick-ness and glandular quantity,promote stem cell homing through anti-fibrotic,anti-apoptotic,and anti-inflam-matory effects,and restore pregnancy function in rats with endometrial injury.Conclusion The synergistic administration of Hyp-NPs and BMSCs could repair en-dometrial injury.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

The present study investigated the chemical constituents from the leaves of Craibiodendron yunnanense. The compounds were isolated and purified from the leaves of C. yunnanense by a combination of various chromatographic techniques including column chromatography over polyamide, silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified by extensive spectroscopic analyses including MS and NMR data. As a result, 10 compounds, including melionoside F(1), meliosmaionol D(2), naringenin(3), quercetin-3-O-α-L-arabinopyranoside(4), epicatechin(5), quercetin-3'-glucoside(6), corbulain Ib(7), loliolide(8), asiatic acid(9), and ursolic acid(10), were isolated. Compounds 1 and 2 were two new compounds, and compound 7 was isolated from this genus for the first time. All compounds showed no significant cytotoxic activity by MTT assay.
Quercetin ; Ericaceae ; Plant Leaves ; Catechin ; Chromatography, High Pressure Liquid

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.
Humans ; Sleep Initiation and Maintenance Disorders/chemically induced* ; Quality of Life ; Sleep ; Hypnotics and Sedatives/pharmacology* ; Antidepressive Agents/pharmacology*