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 investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Objective To investigate the feasibility and safety of bedside transesophageal echocardiography(TEE)-guided atrial septostomy in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods Eight patients(2 females and 6 males)who developed pulmonary edema during VA-ECMO treatment between January 2020 and October 2024 were enrolled.All patients underwent bedside TEE-guided atrial septal puncture,followed by gradual balloon dilation using an Inoue balloon(diameter:18-24 mm).The endpoint for dilation was defined as mean left atrial pressure＜15 mmHg.Post-procedure evaluation included assessment of the septal defect size,mean left atrial pressure,and improvement in bilateral pulmonary edema.Results The mean age of all 8 patients was(43.50±16.84)years old.Atrial septostomy was successfully performed in all patients.The mean balloon dilation diameter was(22.75±2.68)mm,resulting in a mean septal defect size of(6.31±0.37)mm.The mean left atrial pressure significantly decreased from(26.63±1.77)mmHg pre-procedure to(12.75±1.28)mmHg post-procedure(P＜0.001).All patients demonstrated marked improvement in bilateral pulmonary edema,and six patients also showed a significant reduction in the severity of mitral regurgitation following the procedure.No procedure-related complications were observed.Conclusions Bedside TEE-guided atrial septostomy is safe and effective for reducing left heart loading during ECMO support and improving pulmonary edema.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.