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.

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00％),vomiting(775 cases/4.98％)and diarrhoea(545 cases/3.50％)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P＜0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P＜0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P＜0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City,and provide reference for tuberculosis control in schools.Methods Screening data of tu-berculosis and tuberculin test(PPD)of freshmen from 156 schools in different regions of Baoding City from Septem-ber 2021 to March 2022 were collected.PPD screening results of students from different regions and different school stages were analyzed and compared.Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis.PPD screening was conducted on 63 939 students.13 821 students were PPD positive,with a positive rate of 21.62％.3 083 students were strongly posi-tive,with a strong positive rate of 4.82％.15 cases of tuberculosis were found,and the reported incidence was 23.46/100 000.PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences(all P＜0.01).Positive rate and strong positive rate in students in different school stages showed upward trends(all P＜0.01).PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences([22.28％vs 17.89％];[4.85％vs 3.62％],both P＜0.01).PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different,respectively([23.94％vs 21.60％];[5.07％vs 3.56％],both P＜0.01).Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen,especially those from boarding schools in plain areas,screening latent Mycobac-terium tuberculosis infection as early as possible,take corresponding measures to prevent and control the spread of tuberculosis,and reduce the risk of tuberculosis.

Objective To observe the value of augmented reality(AR)navigation system for assisting CT-guided puncture of pulmonary nodules in dog models.Methods Five healthy dogs were selected,and 4 target lung rings were implanted in each dog to build pulmonary nodule models.Deferring to crossover design,CT-guided punctures were performed with or without AR navigation 2 and 4 weeks after successful modeling,respectively,while punctures with AR navigation were regarded as AR group and the others as conventional group,respectively.The time duration of puncturing,the times of CT scanning,of needle adjustment,and the deviation distance between needle pinpoint to the center of pulmonary nodule shown on three-dimensional reconstruction were compared between groups.Results The duration time of puncture in AR group and conventional group was(13.62±5.11)min and(20.16±4.76)min,respectively.In AR group,the times of CT scanning,of needle adjustment,and the deviation distance was 2.40±0.50,2.75±0.44 and(2.94±1.92)mm,respectively,while in conventional group was 3.10±0.64,3.70±0.57 and(4.90±3.38)mm,respectively.The introduction of AR navigation was helpful to shortening the duration of puncture,reducing times of CT scanning and needle adjustment,also decreasing positioning error of needle pinpoint(all P＜0.05).In contrast,the variance of puncture sequences and dogs had no obvious effect on the results(both P＞0.05).Conclusion AR navigation system could improve accuracy and efficiency in CT-guided puncture of pulmonary nodules in dog models.

Objective To investigate the family aggregation of human hookworm infections in Sichuan Province and to identify its influencing factors, so as to provide insights into management of hookworm infections. Methods Three to four counties (districts) were sampled from basins, hilly regions and mountainous regions around the basins in Sichuan Province from 2017 to 2022 as fixed survey sites, and 17 to 30 counties (districts) were selected as mobile survey sites. At least 1 000 permanent residents at ages of 3 years and older were sampled from each survey site, and hookworm eggs were detected in human stool samples using the Kato-Katz technique. Subjects with 2 and more family members and at least 2 individuals diagnosed with hookworm infections in the county (district) where they lived were selected, and the familial aggregation of hookworm infections was analyzed using the test of goodness of fit for binomial distribution. In addition, the knowledge and practice of hookworm disease control were investigated among residents in Hejiang County and Wutongqiao District, Leshan City, Sichuan Province in 2021 and 2022, and the difference in the knowledge and practice of hookworm disease control was compared between members with and without familial aggregation of hookworm infections. Results A total of 66 812 residents from 25 196 households were sampled from main endemic areas of hookworm diseases in Sichuan Province from 2017 to 2022 for detection of hookworm infections, and 4 403 infections were identified (6.59% prevalence). The distribution of human hookworm infections in Sichuan Province did not fit the binomial distribution, and showed family aggregations (χ² = 2 116.759, P < 0.001). Family aggregation of human hookworm infections was found in endemic areas with 1% and higher prevalence of human hookworm infections (χ² = 136.006 to 428.738, all P values < 0.001), and family aggregation of human hookworm infections was identified in different years (χ² = 87.615 to 471.838, all P values < 0.001) and in different terrains of endemic areas (χ² = 8.423 to 1 144.176, all P values < 0.001). The members with hookworm infections had median eggs per gram of 180 (interquartile range, 780) in aggregated families and 72 (102) in non-aggregated families (Z = −2.686, P < 0.05). The proportion of members in families with aggregation of hookworm infections who knew the preventive measures of hookworm disease was significantly lower than in non-aggregated families (24.49% vs. 51.72%; χ² = 10.262, P < 0.05), and the proportion of members in families with aggregation of hookworm infections who often worked barefoot on the ground was significantly higher than in non-aggregated families (30.61% vs. 13.25%; χ² = 6.289, P < 0.05). Conclusions There is a familial aggregation of human hookworm infections in Sichuan Province, and awareness of preventive measures for hookworm disease and frequent working barefoot on the ground are associated with familial aggregation of hookworm infections.