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.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To explore clinical outcomes and bone resection of interlaminar fenestration decompression and u-nilateral biportal endoscopic(UBE)technique in treating lumbar disc herniation(LDH).Methods A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021.Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3)years old,were treated with UBE,29 patients withL4.5and 25 patients with L5S1.There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of(39.9±10.0)years old,were treated with small fenestra-tion,25 patients with L4.5 and 26 patients with L5S1.Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups.Visual analogue scale(VAS)and Oswestry dis-ability index(ODI)were compared between two groups before operation and 1,3,6 and 12 months after operation,respective-ly;and modified MacNab evaluation criteria was used to evaluate clinical efficacy.Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups.Results All 105 patients were successfully completed operation.Both of two groups were followed up from 6 to 12 months with an average of(10.69±2.49)months.Oper-ation time,postoperative time of getting out of bed and hospital stay were(58.20±5.54)min,(2.40±0.57)dand(3.80±0.61)d in UBE group,and(62.90±7.14)min,(4.40±0.64)d and(4.40±0.64)d in small fenestrum group,respectively;and had sta-tistically difference between two groups(P＜0.05).Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery(P＜0.05).VAS of lumbar pain in UBE group(1.37±0.49)score was lower than that of small fenestration group(2.45±0.64)score,and had statistically difference(t=9.745,P＜0.05).Postoperative ODI in UBE group at 1 and 3 months were(28.54±3.31)％and(22.87±3.23)％,respectively,which were lower than those in small fenestra group(36.31±9.08)％and(29.90±8.36)％,and the difference was statistically significant(P＜0.05).There were no significant difference in VAS and ODI between two groups at other time points(P＞0.05).According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group.In small fenestration group,35 patients got excellent,12 good,and 4 fair.In UBE group,amount of bone resection on L4,5 segment was(0.45±0.08)cm3 and(0.31±0.08)cm3 on the segment of L5S1.In small fenestration group,amount of bone resection on L4.5 segment was(0.57±0.07)cm3 and(0.49±0.04)cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group(P＜0.05).In UBE group,retention rate of laminoid complex on L4,5 segment was(0.73±0.04)and L5S1 segment was(0.83±0.03),whileL4,5segment was(0.68± 0.06)and L5S1 segment was(0.74±0.04)in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P＜0.05).Conclusion Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher eficiency,faster postoperative recovery and less damage to bone structure.

OBJECTIVE: Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis. METHODS: The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting. RESULTS: Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment. CONCLUSION Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.
Humans ; Transforming Growth Factor beta/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; RNA, Long Noncoding/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; MicroRNAs/genetics* ; Hepatic Stellate Cells/pathology* ; Liver Cirrhosis/metabolism* ; Cell Proliferation ; Transforming Growth Factors/pharmacology*

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.
Humans ; Ischemic Stroke/drug therapy* ; Brain Ischemia/drug therapy* ; Medicine, Chinese Traditional ; Stroke/drug therapy* ; Headache/drug therapy* ; Drugs, Chinese Herbal/therapeutic use*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I²=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I²=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I²=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I²=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I²=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I²=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I²=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I²=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I²=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I²=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I²=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I²=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I²=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).
Acupuncture Therapy ; Aphasia/rehabilitation* ; Humans ; Ischemic Stroke ; Language ; Prostate-Specific Antigen ; Randomized Controlled Trials as Topic ; Stroke/therapy*